Qia and the monsters

Qia is three. She is scared.

“Don’t be scared or go to your room.”

Qia wants help. She is scared of the monster, FEAR, the giant monster, but her father won’t listen. She sniffles and tries, but she can’t stop crying. She goes to her room, because her father has turned his back. Her mother is drawing. They are busy. They don’t like it when she is scared.

FEAR is enormous and pushes into the room with her. She cries harder in her room with the door closed. No one can hear her now except FEAR. FEAR is large and has horrible drippy teeth and too many arms and keeps swatting at her. Qia gives up and lets FEAR swat her. She sits on the bed with her knees up and puts her head on her arms.

FEAR rages around her room.

After a while Qia is tired of crying. She lifts her head off her arms.

FEAR is smaller. Still bigger than her father, bigger than her mother, but just standing and looking at her. FEAR looks tired too.

Qia pats the bed beside her. FEAR hesitates and looks scared. Qia waits. FEAR shuffles over and sits beside her on the bed.

The room is very quiet. Qia finds a scrap of tissue and blows her nose. She looks sideways at FEAR.

FEAR’s head is down and FEAR seems to be crying. Qia reaches out and takes FEAR’s paw. One of the paws. There are a lot.

FEAR holds her hand tightly and then leans against her. Qia wiggles over a bit more to give FEAR room. FEAR sighs and then snuggles down onto the bed, massive drippy toothy head in Qia’s lap.

Qia strokes FEAR’s fur. It is very soft and dark purple.

FEAR is the first monster that Qia makes friends with. There are many more.

_________________

I was thinking about this story even before the Ragtag Daily Prompt: bugbear.

Negotiating peace

I spend a long day wrestling with love
arguing with myself back and forth
I am no angel descended from above
Those undeserving of my love make me wroth
yet my core argues that it still loves them
and agrees their cruelty’s beyond the pale
I snarl and cough and choke on bitter phlegm
Defend my self staying far away and hale
My core agrees I shall not tolerate abuse
Forgive yet we despair we’ll ever reconcile
They show no guilt nor shame for their misuse
My core says let them be: she is so mild
Negotiation done: Agreed. I may love those who I love
But I leave contact with them to the angels and Beloved.

_____________________

Sonnet 10

Embodying a dream

I wrote about the two dreams I had one night, with seven people. Two babies, a boy and a girl. Two professionals, a woman physician and a male policeman. Two rebels, a woman and a man, the man lying or at least misleading the rebel woman. The rebel woman trying to do something that she suddenly realizes is not important and is, in fact, foolish and dangerous. And a quiet woman.

I have been thinking about the quiet woman ever since. My Meyers-Briggs type in medical school came out INTJ, but we are not one thing or another. We have preferences, but we all have to use all the skills. I can be extroverted. I had to work on feeling, that was the really difficult one for me after a frightening childhood. I can pay attention to facts though I sweep them into the intuition very quickly. Medical school is facts and facts and facts, except then there are parts that turn out to change as science changes.

The eighth person is a quiet man. He is not present in the dream. I am thinking about him. I wonder if I will have another dream when I am ready.

I am attending some workshops on line for treating trauma. It is quite fascinating. They talk about working with clients who have aspects like my dream: a small child with trauma. A “fake adult”, aka “adaptive child”, with the tools that the child develops to survive in their childhood. Helping the “fake adult” recognize that some of coping tools may not be helpful or necessary any longer. First, they thank the “fake adult”, for protecting the traumatized child and for surviving at all and for not giving up. I think this is so important, to acknowledge that we have to thank that part of ourselves that did what it had to, that did what it could, to survive. And this can include things that we are ashamed of or fear that others would hate us for if found out. We had a temporary doctor at the hospital who described being a boat person escaping Vietnam at age 8. They were picked up by pirates. “We were glad to see the pirates, because we had run out of water. If the pirates had not picked us up, we would have died.” So there is perspective: death by dehydration or pirates? And she went from a refugee camp and then through medical school and became a physician. Survival and success and I hope that she is thriving.

I like it when a dream has such recognizable symbols. My now retired Unitarian Universalist minister says that we can sit with dreams for a time. What do the symbols mean to me? What is the dream telling me? My dream is in part telling me that I do not need to have the rebel woman lead: she can rest and let the quiet woman take over. And that I am very tired of rebel men who mislead me or run away. I woke up and thought, oh, yes, I see! I am tired of that and ready for change.

Change and transformation can happen throughout our lives, at any age. I welcome it.

Blessings and peace you.

___________________

The photograph is Sol Duc and Elwha enjoying doll bunkbeds. And acting like siblings do sometimes. And then they curl up together.

Practicing Conflict

An essay from my church talks about the writer avoiding conflict, fearing conflict and disliking conflict. This interests me, because I do not avoid conflict, I don’t fear conflict and actually, I like it. Our emeritus minister once did a sermon in which he said that when you are thinking about two conflicting things at once, that is grace. I have thought about his words many times, especially when I am not in agreement about something.

Does this interest in conflict mean I fight all the time? Well, sort of, but not in the way you think. I don’t fight with other people much. I fight myself.

What? No, really. Most topics have multiple sides. Not one, not two, but many. Like a dodecahedron or a cut gem. Hold it up to the light, twelve sides, each different. I argue the different sides with myself.

I learned this from my parents. My parents would disagree about something, they would discuss or argue about it, and then they would bet. Sometimes they bet a penny, sometimes a quarter, sometimes one million dollars. Then one of them would get up and get the Oxford English Dictionary, or the World Atlas, or some other reference and look it up. This was pre-internet, ok? 1970s and 1980s.

Sometimes my parents would even pay each other. The penny or quarter. My father spoke terrible French and my mother had lived in Paris for a year after high school, so he could get her going by insisting that his French was correct. It wasn’t. Ever.

There were other arguments in the middle of the night that were not friendly and involved yelling, but the daytime disagreements were funny and they would both laugh.

Once my sister is visiting after my mother has died. My father is present. My father, sister and I get in a three way disagreement about physics. I’m a physician, my sister was a Landscape Architect and my father was a mathematician/engineer, so we are all three talking through our hats. However, we happily argue our positions. Afterwards, my gentleman friend says, “That was weird.” “What?” I ask. “That was competitive and you were all arguing.” “It was a discussion and we disagreed.” “I won’t compete.” “We let my dad win, because it makes him happy.” “That was weird.” “Ok, whatever.”

My gentleman friend is also shocked when my teen son challenges me at dinner. My son says, “I am researching marijuana and driving for school and there isn’t much evidence that it impairs driving.”  I reply, “Well, there is not as easy a test as an alcohol test and it was illegal, so it has not been studied.” We were off and having a discussion.

Afterwards my gentleman friend says, “I am amazed by your son bringing that up. We weren’t allowed to discuss anything like that at dinner.” I say, “We pretty much discuss anything at dinner and both my kids are allowed to try to change my mind. About going to a party or whatever.” He shakes his head. “That is really different.” “Ok,” I say.

This habit of challenging authority, including adults, did not go over well when my son was an exchange student to Thailand. It did not occur to me to talk to him about it. He figured it out pretty quickly.

Back to my internal arguments. If I take a position, I almost immediately challenge it. I think of it as the old cartoons, with the angel on one shoulder and the devil on the other. The devil will make fun of things and suggest revenges and generally behave really badly. The angel will rouse and say, “Hey, you aren’t being nice.” Then they fight. The internal battle very quickly becomes comic with the two of them trading insults and bringing up past fights and fighting unfairly. When it makes me laugh inside, I can also be over the driver who cut me off, or someone who spoke nastily, or whatever. My devil is very very creative about suggested revenges. When the angel says, “You are meaner than the person who cut you off!” I am over it.

When I was little and disagreeing with my family, my sister could tell. “You have your stone face on!” That meant I was attempting to hide a feeling, especially fear or anger or grief. Siblings and family are the most difficult because they can read us and see through us like glass. My physician training also teaches control of feelings. I have sometimes wanted to grab a patient and scream “Why are you doing this to yourself?” but that really is not part of the doctor persona. I am doing it inside, but I can put it aside until later. Then the devil goes to town! And the angel tries to calm the devil down.

Maybe we all need more of this skill. Pick a mildly controversial topic. Argue one side of it. Then switch positions and argue the other side. Go back and forth until it gets ridiculous. Let each side get unreasonable and inflammatory and annoying. This can play in your head and not on your face. Once you can do a mild topic, move on to something a bit more difficult. If you only know the arguments on your side, read. You can find the other side, the internet is huge. Start gently.

A friend says, “You always argue about things.” I say, “I prefer to think of it as a discussion.” “You always take the other side.” “Well, it interests me. And if there is no one to discuss something with, I discuss it with myself!” “Weirdo,” says the friend. I think he’s jealous, really I do. Don’t you?

Family

The photograph is from left to right, my sister Christine Robbins Ottaway, my (sort of but not blood) cousin Katy, and me. This is a fourth of July. We wanted to DO something. We were at my maternal grandparents’ in Trumansburg, New York. My mother suggested that we dress up and do a presentation. We wore her 1950s prom dresses, held a small parade involving three dogs and a cat who were also in costume, and read the Declaration of Independance and the Preamble to the Constitution to a group of adults in lawn chairs. This was in lieu of fireworks. We had fun but we still missed fireworks.

I am thinking about asking. I could not ask my mother for specific things I wanted as a child. She would get me a different and cheaper alternative. If I was disappointed, I would be guilt tripped or humiliated. I did not ask my father for things either. He would make and break promises, too sick from alcohol or he would have forgotten. I stopped asking because I did not like being disappointed and I did not like being shamed. Once I really really wanted something for Christmas. My sister and I made a quiet deal, showing each other exactly which toy we longed for. Then we each shopped with our mother and insisted on the toy the other wanted. Our mother did try to talk each of us out of the toy. We had arranged it so that we were spending the same amount of money: $20. She thought that was outrageous and that something cheaper would do just as well. We both stood our ground on the other’s behalf and then open the presents on Christmas day with faked surprise and real joy. We did NOT tell our mother.

On an earlier Christmas I sewed my sister a toy stuffed snake. My mother was discouraging, but she let me have cloth and needle and thread. “Why do you want to make her a snake? A snake?” I couldn’t really explain well. We had gone to a county fair and my sister and I both longed for the velvet snakes, six feet long and deep red. The snake I made for my sister was only a foot and a half long and I had flowered fabric, not velvet. I coiled it in a circle and wrapped it. My sister was delighted with it and held it all Christmas morning. My mother just shook her head. “A snake.” she muttered.

The things that I could ask for were books and music. I was the kid that the teacher would hand the scholastic book box to after she handed out one or two books to the other kids. I would order 20 books. My father said I could have as many as I wanted as long as I read them all. The only books I avoided were about television or movies. I loved a non fiction book about WWI Flying Aces. The technology of the airplanes and the problem of bullets ricocheting off the propeller were amazing. I also liked that it talked about the ACEs on both sides: German, English, French, American.

For the Ragtag Daily Prompt: ask.

I don’t know who took the photograph. I think it was one of my grandparents. Oh, I think “cousin” Adam is in the picture too, though he is nearly hidden behind the flag.

Adverse Childhood Experiences 14: Hope

I keep reading bits about despair and about how a generation of children is being “ruined” by the pandemic.

Not so, I say. There is hope. We need to support each other to survive and then to thrive.

This generation WILL have a higher than average ACE score. If the Adverse Childhood Experience scale is from zero to eight, children in this time period will have at least one higher point than average and many will have three or four or more. Loss of a parent, a sibling, beloved grandparents during covid. Increases in domestic violence, child abuse and addiction. These are all part of the ACE score.

What does this do to children? They have survival brain wiring. They will do their best to survive what is happening. A friend and I both have high ACE scores, 5 or more, and we are both oppositional defiant. We showed this in different ways. He grew up in the same community. He escaped from home and knew all the neighbors. He walked to the local church and attended at age 3 or 4. He has lived in this community all his life.

His oppositional defiance showed up at home, where he consistently refused to obey. And in school, where he confounded and disobeyed teachers and passed anyhow.

My family moved every 1-5 years. I hated moving. I wouldn’t talk to kids in a new school for a year. It was very difficult. So my oppositional defiance was very very internal. I hid in books and in my head. In 6th grade I got in trouble for hiding novels inside the school book I’d already read. I also would just not listen and my respect for the teacher got even lower when she would be angry that I knew the answer to the question once she’d repeated it. I wasn’t listening because I was bored. She was the first teacher that I thought, well, she is not very bright. The next year they stuck me in the honors class and I stopped being bored, though I still questioned practically every opinion every teacher had. I wanted evidence and I did not believe it just because the teacher said it.

I am not saying that oppositional defiance is in every high ACE score. I don’t know that. Why oppositional defiance? Imagine you are a small child and you are beaten. There isn’t rhyme or reason. You can’t predict when the adult will be out of control. Why would you behave “well” if it makes no difference? You might as well do what you want, because nothing you do will change the adult. Or imagine you are a small child who is with one person, passed to another, then to another. You may not exactly trust adults after two or three repetitions. And you want to survive.

There is an increase in addictions, behavioral health diagnoses, and chronic illness in adults with a high ACE score. A researcher when I first heard a lecture about it said, “We think perhaps that addiction is a form of self medication.” I thought, oh, my gosh, how are we ever going to treat THIS? Well, we have to figure that out now, and we’ve had 30 years to work on it.

I was very comfortable with the oppositional defiant patients in clinic. I got very good at not arguing with them and not taking their behavior personally. They might show up all spiky and hostile and I might be a little spiky and gruff back: sometimes that was enough. I think the high ACE score people often recognize each other at some level, though not always a conscious one. With some people I might bring up ACE scores and ask about their childhood. Sometimes they wanted to discuss it. Sometimes they didn’t. Either was ok.

One thing we should NOT do is insist that everyone be “nice”. We had a temporary doctor who told us her story. Her family escaped Southeast Asia in a boat. They had run out of water and were going to die when they were found by pirates. The pirates gave them water. They made it to land and were in a refugee camp for eight years or so. She eventually made it to the US. She was deemed too “undiplomatic” for our rural hospital. I wondered if people would have said that if they knew her history and what she had been through. It’s not exactly a Leave it to Beaver childhood, is it? When she was telling us about nearly dying of thirst in the boat, my daughter left her chair and climbed on my lap. She was under ten and understood that this was a true and very frightening story.

We can support this generation of children. This has been and is still being Adverse Experiences for adults as well. Family deaths, job loss, failure of jobs to support people, inflation. Remember the 1920s, after World War I and the last pandemic, of influenza. “On October 28, 1919, Congress passed the National Prohibition Act, also known as the Volstead Act, which provided enabling legislation to implement the 18th Amendment.” (wikipedia). There were forces trying to legislate behavior, as there are now. The result in 1920s of making alcohol illegal was speakeasies, illegal alcohol, and violence. Some people acted wild after WWI and the influenza pandemic and some people tried to lock down control, by controlling other peoples’ behavior. It did not work then and it will not work now. The wildness is out of control grief, I think, grief dysfunctional and drinking and shooting and doing anything and everything, legal or not. We remember how the 1920s ended too. Let us not repeat that. Let us mourn and grieve and support each other and support each other’s decisions and autonomy.

Blessings.

Adverse Childhood Experiences 13: on gratitude

I saw a meme today about gratitude. It is saying that some people look at a garden and see thorns and weeds, but others see the roses. That we need to have gratitude. I think this is simplistic and papers over the trauma and grief that some people have. If they have endured a highly traumatic childhood, who am I to say they should focus on the roses? They may have a very good reason to see if there is something like a thorn that can hurt them before enjoying the roses.

I work with many patients with high Adverse Childhood Experience scores and mine is high too. I don’t tell my patients that they should have gratitude. I tell them “You survived your childhood. You have crisis wiring. Good for you. Some of your learned crisis survival wiring may not serve you as well now as it did when you were a child.” Then we discuss whether they want to work on any aspects and the many many different approaches. One example: a man who sleeps very lightly. He said that it was lifelong. When asked about his childhood he says, “We would have to leave in the night when there was shooting in my neighborhood. It was a very dangerous area.” I said, “I am not surprised you sleep lightly. You HAD to in childhood to survive. Is this something you want to try and change?” He thought about it and decided, no. Once it was framed as learned in childhood to survive, he stopped worrying about “normal”. He was satisfied that the way he slept was “normal” for him and he wanted to wake up if he heard shooting.

I think we have to ask why a person sees thorns and weeds in a garden before we judge them. My first thought with a new and angry or hostile patient is always, oh, they have been badly hurt in the past. What happened? I don’t worry that the anger is at me. I know it’s not at me, it’s at the system or a past physician or a past event. Under the anger there are other emotions, usually fear or humiliation or grief. I have brought up Adverse Childhood Experience scores on the first visit sometimes. One person replies, “I am a 10 out of 10.” The score only goes up to 8 but I agree. He was a 10. He stated once, “The military loved me because I could go from zero to 60 in one minute.” Very very defensive and very quick to respond. The response may seem extreme and inappropriate to other people: but it may feel like the only safe way to be to my patient.

I grew up hiding any grief or fear in my family, under anger, because grief or fear would be made into a story told for laughs. In college, a boyfriend told me I was an ogre when I was angry. I started working on it then and it was difficult to tame that. The person who took the longest was my sister: she could make me explode until I was in my residency. Medical training was excellent for learning emotional control, at least, on the surface. After my mother died, I had to do the next piece of emotional work: open the Pandora’s Box of stuffed emotions, mostly fear and grief, and let them out. It was such hard work that my day where I saw the counselor for an hour was harder than my ten hour clinic day. I did the work, for two long years. Blessings on the counselors who stood by me while I worked through it.

I do not think we are ever done with that sort of work. I think, what do I need to learn next? What is this friend teaching me? Why is this behavior frustrating me and I have to look in my inner mirror. Why, why, why?

Blessing on your healing path and may you not be judged.

Link about ACE scores: https://www.cdc.gov/violenceprevention/aces/about.html

Sometimes I do feel like a fossil, now that I am middle aged. For the Ragtag Daily Prompt: fossil.

playing telephone

If they whisper from one end to the other, does it get garbled before it reaches the other end?

Isn’t gossip a sin?

For the Ragtag Daily Prompt: chaos.

first impressions

I am taking a writing class and our next book is on cultural appropriation.

This interests me. I tend to be a little gender blind and race blind when I meet people. I am using my super skill instead. My skill is developed from a really scary childhood: I read the stuffed emotions. The stuff people are hiding.

No way, you say. Oh, yes, I say.

My sister described coming home from high school and stopping when she walked into the house. She was trying to sense what was going on. Were our parents fighting? Was our father drunk? Yes, he was drunk, but which stage?

We talked about the stages and which we hated most.

Stage goofy/silly was annoying but not toxic. We said we had homework.

Stage asleep in a fetal ball in the upstairs hallway. My sister said she would step over him to get to her room.

Stage maudlin. We both agreed this was the worst. He would cry and say, “You can tell me anything.” Once he caught me in that stage and I was in tears by the time my mother got home. I left the room. The next morning mother said, “He said you two were discussing the cat’s disappearance.” I didn’t answer. We never said a word about the cat. I didn’t know if he was lying or was too drunk to remember it the next day, so made it up. Don’t care. Avoid.

He was never physically abusive. He and my mother would scream at each other at 1 or 2 am through most of high school. Reading her diaries, she writes that she drinks too much. I think they were both alcoholics, thought the family story is that he was the bad one. But I can’t imagine yelling with a drunk at 1 or 2 am for an hour. What is the point? They are drunk. So either she was drunk too or needed to fight.

Emotionally abusive, yes, both parents. My mother would take any show of fear or grief and tell it as a very very funny story to every person she ran into. Is it any surprise that I had to go into therapy after she died to learn to feel fear or grief? My sister would say, “She’s got her stone face on,” about me. Um, yeah, I am NOT going to let my family see my emotions…

Anyhow, that is what I read in people when I first meet them. It’s not the suit, the clothes, the make up, the race, the gender. I pretty much ignore those. I was fashion blind in junior high, a girl geek, could not read the code and did not care. I had given up on socializing with my fellow students. I was hopelessly bad at it. I did a lot better with the adults around my parents. I could have actual conversations with them.

I had one patient who was transgender where I couldn’t remember which direction. I didn’t care, either. That was a really angry person. Anger is always covering other emotions, so I avoided pronouns and tried to be as gentle as possible.

I complained to a counselor once that I can’t turn this “off”. And that it’s fine in clinic with patients, but it screws with my relationships with my peer doctors. They do not like it if I “read” them.

It took me years, but I finally realized that I have to use my clinic skills with everyone. I can’t turn off “reading” any more than you turn off your eyes when you meet a new person. But I can be as gentle with everyone as I am in clinic. I realized that as I started on a trip and the trip was amazing, everyone was so nice.

This reading is a product of a high ACE Score: Adverse Childhood Experiences. I score about a 5. One of my patients set off my ACE alarms on the first visit. I asked if he had had a rough childhood and gave a very short explanation of ACE scores. “Oh, I am a ten out of ten,” he said. He was, too. Ran away from home at age 6 or 8.

The ACE scores of all the children are rising from the last two years. The war will raise them even more, worse for the children there and the kids trying not to starve in Afganistan and Syria and world wide.

It will be interesting to read about cultural appropriation. But I don’t care much: I don’t “see” those things when I meet someone.

Hugs and blessings.

The photograph is me and my sister Chris in 1987, before my wedding. We were dancing before the wedding. She died in 2012 after 7 years of breast cancer.

Doctors and nurses and hospital staff are the last caregivers for the elderly alcoholics and addicts who are alone, whose families have finally cut them off. I think this song illustrates their pain. We try to take care of them.

Update on Addiction 2022: Mouse Cocaine Addict Studies

Recent experiments on mice are giving us interesting information on addiction, and suggesting that l-dopa may be able to control/mitigate addiction. This lecture about how dopamine works in addiction using a mouse model (poor mice) blew me away. The mice fell into two categories: maintenance users and vulnerable addict rats. The study of the dopamine postulates a reason for the difference.

20th Annual Drug Conference Washington State from 2019

Notes from lecture 3: Paul Phillips PhD
Dopamine Neurotransmission in Substance Use Disorders: from Preclinical studies

For a long time there were no agreed upon animal models: rats don’t steal money from other rats to buy drugs. However, rats do get addicted and this can be studied.

There are features in rats, rat behavior and rat brains that might translate to humans.

1. Basic discoveries about dopamine neurotransmission in substance use disorders is discussed.
A neurotransmitter study checking every ten minutes in brain examines two areas: dorsal and ventral striatum. Dopamine is increased in the area between cells from the administration of substances “first time use” in animal models: cocaine, alcohol, methadone, cannabinoids, nicotine, amphetamine, morphine. This is the first clue re addictive drugs, whether there is an increase in dopamine intraneuronally. The endpoint is that direct effect on dopamine receptors, which has a different brain mechanism for each drug. Cocaine blocks the receptor that reuptakes the drug into the neuron. Methamphetamines and amphetamines reverse the reuptake pump, makes the receptor spit it out. Gaba neurons act to inhibit dopamine neurons, normally mu receptors on the gaba interneurons and the opioids block those. Ethanol has another mechanism of action. It changes inhibitory activity, lowering the inhibition of the gaba interneurons. Nicotine REALLY messes with multiple receptors and multiple cells, but main effect is increase of dopamine in the striatum.
Increased dopamine in human brain relates to the feeling of being high: brain PET scans show amphetamine and dopamine bound less, reduction in the binding. Subjects were substance abusers. Subjective questioning of how high they felt correlated with the amount of dopamine released on the PET scan. Methylphenidate was used in that study. Canada study: cocaine increases dopamine in human brain by PET scan.
Addiction does lead to changes in the brain, on both PET scans and functional MRIs.
PET scans measuring dopamine binding in the brain show that the baseline in brains of substance abusers differs from non-abusers. The levels of dopamine receptors is lower in the substance overuses and there is lower binding than controls: heroin, alcohol, meth, cocaine (and obesity and ADHD…..). (This has been known for opioid overuse and chronic use for a while: the brain cells withdraw receptors, so the same dose does not reduce pain because there are less receptors. The change in receptors appears to vary in different subjects. Recovery is very slow.)
The role of dopamine has been confusing. It is known that it is involved in the cue evoking cocaine “craving”, but is also involved with — satiety. This has been confusing and contradictory — what does dopamine do but also the dynamic structural signaling.

2. The animal studies demonstrate that the dopamine signals are phasic.
Rat studies measure changes in dopamine minute to minute electrochemistry for sub-second dopamine detection in vivo, which means we can measure changes in dopamine in real time. There is an identified output signature for dopamine levels, measure in 8.5 millisecond, ten measures per second.
The rats were voluntarily taking cocaine. The cocaine was available in a liquid with a light that would come on when it was available, for two hours daily. The animal presses a lever when the light cue is on and gets an infusion of drug. With the ten measures per second, the first and smaller dopamine response in the brain is before the lever is pressed. That is, there is a rise in dopamine BEFORE the rat presses the lever. If stimulated dopamine, the animal would go press the lever. Then there is a larger reward dopamine signal when the drug hits.
Dopamine is the chicken and the egg: signal to USE and signal that has ARRIVED.

3. Changes that take place with drug use
There is a signal change over time that correlation with features of addiction.
The mice had an implanted brain electrode, tinier than human hair, 7 microns, biocompatability — don’t make the brain attack it as a foreign object so rat brain keeps working. The study involves tyrosine hydroxylase, a precursor of dopamine. A food pellet response of the tyrosine remains the same at 1, 2, 6 months so can monitor substance abuse brain changes. These are cocaine addicted rats. They get cocaine via a nose poke of a button when it lights up. Pellets, not iv (they learn that faster). There are 2 ports to nose poke: active and inactive. The signal that cocaine is available and the pellet is active: a light comes on for 20s and then drug arrives. Can take again after 20sec. The rats titrate cocaine use: not continuous. They pace cocaine use, wait for it to wear off. Over time, drug use 1 hour access daily… slow increase, relatively stable.
When the access is bumped up to 6 hours access daily… rats do increase use — first of 6 hours, escalation of drug use faster — in humans development of tolerance.
With 1 hour cocaine availability, the dopamine response to the cocaine in the rat brain is lower by the 2nd and 3rd week, slowly decreases, then with 6 hours of access the loss of dopamine is very robust, happens faster, dopamine signal gets smaller every time.
Rats long access: were there individual differences? Yes, metric, nonescalated vs escalated groups so like humans. 60 escalated 40 didn’t and stayed stable. So essentially I named these “Vulnerable addict rats” and “Maintenance rats”.
Which group most motivated to take cocaine? The study ups the price of cocaine for rats, how many times are you willing to receive the drug? The escalating animals made more responses, “worked harder” for the drug. The escalator brains, Vulnerable Addict Rats, had just about a complete loss of dopamine signal by three weeks.
The nonescalators had more stable dopamine responses, retained some dopamine brain function.
The greater the loss of dopamine, the more the animal escalates the drug use.
The Vulnerable Addict rats would use cocaine to the exclusion of food, water, sex and sleep and died early.
This is a feedback loop. The rats get a success signal when the drug is taken — but over time don’t get the success signal because dopamine receptors are gone — so take more. In the Vulnerable Addict escalators, the dopamine signal of anticipation goes down in response to the cue, the drug effect takes a little longer but the pharmacological response to drug actually remains.
They tried giving l-dopa, a parkinson’s drug and if treat, the rats get a restoration of the dopamine cue — pharmacological response didn’t change — how does this affect behavior? A daily shot of l-dopa and the animals on the l-dopa have less escalation. (wow!) The l-dopa didn’t affect the nonescalators/maintenance rats. When they remove the l-dopa in the vulnerable addict rats, the animals jump to higher use and so the brain changes are happening even when it is masked by the l-dopa but does not stop the brain changes.
They ask the question: can you reverse escalation? With the the l-dopa, they use less.
Dopamine signaling to take drugs (the anticipation cue when the light goes on) decreases in animals that escalate drug taking, but does not change in animals with stable drug taking.
Restoring dopamine signaling with l-dopa can prevent or reverse escalated drug taking.
This dopamine signaling….

4. Mechanisms — drug cue elicits dopamine.
So this is about triggers. This is a paired drug cue: the light signals that the drug is available. If a non-contingent drug given to animal, the light still elicits drug seeking. Using a naive animal: pair reward with cue, over time the cue will increase dopamine.
(hmm. Facebook. blogging. Instagram. “You have mail”. )
The initial addiction has a short access time. One hour out of 24. When this is changed to long access, some animals escalate vs non escalation — as take more and more drug, the response to the drug taking cue gets larger in the escalators/Vulnerable Addicts. Presentation of cue — by investigator vs animal:
If elicits drug seeking than the dopamine response gets larger to the cue over time.
If the cue is given but other choices of liquid, then the dopamine response gets smaller in some rats — so terminating drug seeking. The Vulnerable Addict Rats had a larger and larger dopamine craving cue spike, the longer they were off the drug. The the increase in the cue drives craving and decrease drives seeking — so both bad.
The conclusion in the rats is that craving for drug, related to cues, is dependent to length of time off drug. The longer the rats were off the drug, the larger the dopamine spike when the cue light comes on. The measure of cue behavior gets worse …. 60 day study in rats, this is not physiological withdrawal, is prolonged way beyond the withdrawal.
1. noncontingent
wait a day or wait a month
work harder to get drug, harder a month out
reaction to drug cue presentation, enhanced over time
at start of drug small signal to drug cue
long access then cue gets bigger
same a day after stop drug
but huge in a month after no drug — huge dopamine response

(my thought was then swearing. how do we treat this?)
In chronic drug use the cue signal shrinks which reinforces drug use AND stopping increases the cue response which ALSO reinforces.

5. Implications for treatment
treating rats
They discuss a virus with promotor that affects dopamine cells, light activated ion channel, cells release dopamine when light stimulated
only activates release of dopamine, to understand mechanisms.
For the self administered nose cue …. In the nonescalator maintenence rats, dopamine cue response stays fairly robust, stimulate those cells and no change.
In the escalator/vulnerable addict rats… if do a virus stimulation of dopamine in the brain, more dopamine to cue boosted, so they use less cocaine and look like the non-escalators.
5th cue less dopamine than 1st cue: if put dopamine back then maintains the drug seeking.

What underlies the decrease in dopamine release?
When the animals use cocaine, dynorphin goes up (kappa antagonist).
They injected a kappa receptor blocker — animal no longer escalate (not in humans at this time, don’t understand well enough) treating animals that are escalating, so the bad addict/vulnerable rats.
Most animals don’t escalate — but pretty serious amounts of drug cocaine so not abstinent.

For future
Dopamine diametric changes: dopamine may reduce consumption but might increase craving, so it is difficult to treat.
l-dopa — treatment — some studies, looking for abstinence, does NOT produce abstinence. Does not make abstinence worse. Says that promise seen relates to the status of the subject — helps with people who are still using (some) but doesn’t help increase or prolong abstinence. So could reduce harm but not abstinent….politically unpopular. Happier with turning alcoholic into a social alcohol user, but that idea is less popular/politically ok with cocaine/opioids (and especially meth).

They are studying mouse nosepokes for alcohol — reduced intake when the rats are on l-dopa.

There is a functional agonist for kappa receptors == buprenorphine, might have effects on drug consumption, speculation across different drugs.

Dynorphin is a stress related peptide, so does that signaling produce escalation of drug taking? So other stress drugs — like corisol, CRF, plan for more studies.

Question: Stress related hormones– babies in stress in utero and in stressful childhood have less dopamine receptors and need more dopamine for pleasure, susceptibility to drug addiction (ACE scores) so is still really early studying neurotransmitters.

Dr. Question: why do people do better with agonist therapy than abstinence in opioids vs other drugs? Answer: we don’t know….. yet.

further information:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1920543/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC80880/
https://archives.drugabuse.gov/news-events/nida-notes/2017/03/impacts-drugs-neurotransmission
https://nida.nih.gov/