Concord

my heart is broken
love doesn’t conquer all
unselfish love
unreturned
unrequited
opens me to wound after wound
some turn from love no matter what
cling to the lies they tell themselves
cling to the poison they embrace
turn from love into the uncaring bottle
turn from love into the insensate smoke
turn from love even to the grave

I wish my heart would let them go
and heal

__________________

My friend Liz took the photograph, half way through the Rainshadow Chorale concert last Sunday.

Alcohol myths

I am back working in Colorado and a recurring theme this month is alcohol and alcohol myths.

Myth: If I only drink on my days off, I am not an alcoholic. Nope. People can binge one day a week and still be an alcoholic. A standard “dose” of alcohol is 12 ounces of 5% beer, 5 ounces of standard wine or 1.5 ounces of liquor. But what if someone drinks 8% beer, 12 ounces? Well, that’s 1.6 standard drinks. An 8% 16 ounce beer? That is 1.6 times 1.3, so 2.08 drinks. Perhaps we should have an app that calculates this. And locks the car ignition when we are over the limit.

How much alcohol means that we are an alcoholic? The guidelines right now in the US say 7 drinks per week maximum for women, 14 for men, no more than one in 24 hours for women, no more than 2 in 24 hours for men and no saving it up for the weekend. Here: https://www.niaaa.nih.gov/health-professionals-communities/core-resource-on-alcohol/basics-defining-how-much-alcohol-too-much#pub-toc3. However, alcohol is bad for the liver, bad for the heart, bad for the brain, and increases cancer risk. There is not a “safe” amount.

What is binging or heavy drinking? For women—4 or more drinks on any day or 8 or more per week, For men—5 or more drinks on any day or 15 or more per week. The rate at which people drink is also part of this.

MYTH: If I don’t throw up, I’m not an alcoholic. Now that’s an interesting one. When we drink, alcohol is absorbed into the blood and goes through the liver. The liver has enzymes which break alcohol down into aldehyde. Aldehyde is a carcinogen, causes cancer. Aldehyde is broken down by other enzymes into acetate and then to carbon dioxide and water. Some people break down the aldehyde quickly, fast metabolizers. They can drink a lot and not throw up because they break the aldehyde down fast. However, the process inflames and kills liver cells. If they keep drinking, the liver slowly dies, and this is cirrhosis. Eventually they will not be able to break down alcohol fast because the liver makes the enzymes. Then they will start throwing up.

Other people make enzymes that are slower or make less, and they get sick and have alcohol poisoning more quickly. The fast metabolizers are at higher risk for cirrhosis and the slow ones for liver cancer, but they can get either.

MYTH: “My blood pressure is fine.” I spoke to a person who stated that their blood pressure was ok during pregnancy so they did not have high blood pressure. The chart shows very high blood pressure for the last three years and I didn’t look back further. I ask, “Did you stop drinking alcohol while pregnant?” “Of course.” When NOT pregnant, this person admits to 4-5 drinks a day. Also, the history in the chart states that they had blood pressure complications in pregnancy. I did not have time to go through the chart and look at that, but this person is in denial. I think of denial as the addiction taking over and the addiction lies. It lies to me but it also lies to the person. They want to believe what they say. They want everyone else to believe what they say even if it is patently a lie and ridiculous. A woman who says a friend gave her something, she didn’t know what it was, for a headache. “How did you take it?” I asked, looking at the urine dip results. “I snorted it.” “So what things do you snort for a headache?” She was positive for cocaine and pleading ignorance was ludicrous. Another person has a positive urine drug screen for multiple things. “Can I try again?” Pause. “Sure.” I say. The first one is a false sample and I am very curious to see what the real sample will have. It has nothing. He is then surprised that I won’t fill his prescription and offer inpatient drug rehabilitation. Come now, sir, you got a urine sample from a dealer when you sold the medicine I gave you for something else. Your dealer must have been annoyed or gave you the wrong sample. When someone is really out of control, they do not have convincing lies and the only person they can convince is themselves. It is interesting to watch someone be all outraged that I do not buy the story, accusing me of discrimination or hating them or hating their race or whatever. They attempt to accuse and distract. It is harder for families because they desperately want to believe their loved one, even when the evidence shouts the opposite.

What does blood pressure have to do with alcohol? Alcohol drives blood pressure up and pulse, especially when it is wearing off. Severe alcohol withdrawal is delerium tremens and people can have such high blood pressure that they have a stroke or a heart attack or encephalopathy — a poisoned brain. They can hallucinate or have seizures and it is very dangerous. “Very dangerous” means they could die or have permanent disability. Tobacco, cocaine, methamphetamines, all raise blood pressure. The number one cause of death in the United States is the heart, but it’s not just from hypertension and weight and cholesterol and inactivity. Addictive drugs have a huge contribution.

There is nothing cheap about the cost of addiction in our country.

For the Ragtag Daily Prompt: cheap.

Content

I never do know where a poem is going when I start it. Usually I start in the dark. To my surprise, those poems will end in the light. Apparently the reverse is true too.

Content

At the moment I am feeling content
deeply content
with monsters

At the moment I don’t need more
then this
me
a few friends
and all the monsters

I can’t fix the monsters
healer, right
the people come
over and over
and won’t admit
their monsters

the monsters sit on the floor
of the exam room
clinging to the person
chained to the person
the monsters wail and cry
while the person
ignores them

It has taken me all these years
to let go of anger
fury
rage
that almost no one
admits to monsters
or tries to heal them

Except the addicts, drunks, crazies
they see them too
many try to destroy their vision
with alcohol or drugs
or persist on telling others
about the monsters
until they are drugged

Yesterday I look on line
for local music
not bluegrass
thinking that I would like
to find a place with grown ups
quiet

I think, how silly I am
to look for grown ups in a bar
and then I try to think
of where to find some grown ups
and I think THERE AREN’T ANY GROWN UPS
it’s all just children
who’ve grown big

I do not like drama
there are no movies
that I want to see

I like clinic
where I try to help a little
sometimes a lot
sometimes a person might remove
one knife
one chain
one arrow
from their traumatized
terrified
bleeding
monster

And really
that is why I am here
and that is all that I can do

__________________________

For the Ragtag Daily Prompt: journey.

Meanwhile, rat joy: https://www.bbc.com/future/article/20241128-i-taught-rats-to-drive-a-car-and-it-may-help-us-lead-happier-lives.

Intimacy

What IS intimacy? And what is love? And are they the same thing? Do you have to be intimate to love someone? Not meaning sex, but what level of intimacy is “normal” and “appropriate”?

I am thinking of my mother. When I was just starting college, she started talking to me about my father and about his drinking. I became more and more uncomfortable and finally asked her to find a counselor or someone other than me. The thing is, she refused to DO anything about his drinking and in fact, covered it up. The two of them would scream at each other at 2 am and fight when I was in high school. It would wake me up and I would think, I wish they wouldn’t, because I have school tomorrow. But I certainly didn’t go say anything because then they would have screamed at me. And as I got older, I wondered if my mother was drinking heavily too. Because why would she argue with someone drunk at 2 am, that makes no sense. Unless she either was drunk or loved to argue or both.

It is clear that she was drinking heavily at that time from her journals. Over and over she writes, I drank too much last night. Hard to blame her for not intervening with my father if she is drunk too. But she was using him as her cover up. Her family blamed him. My grandmother, her mother, didn’t blame him. She loved them both.

When we had guests, my mother would turn on the charm. She could mesmerize a room and entertain people with stories. My sister and I and others would be the butt of the stories. My father too. After the guest left, she would often talk about them. Analyze them. Talk about their faults and weaknesses. I was fascinated but a bit horrified too. She seemed to like these people so much and to charm them and invite them back, but was talking about them behind their backs. Ick.

So intimacy interests me. I wonder how to do it “right”. Maybe right is not the best word. How to do it “functionally”. I really don’t know what normal is, my maternal family certainly did not model healthy intimacy. My generation still gossips about each other. I quit that at age 19 and refused to be part of it. I don’t think anyone saw my rebellion except my maternal grandmother. She did not say a word but I knew that I had her respect. She did not play the family game with me.

I don’t think that gossip and triangulation are a good form of intimacy or love. Person A talks to person C about person B. Word gets around and sometimes it is person D that says something to person B and person B gets upset when they realize where this came from. And how twisted and one sided the story is. And aren’t we seeing this play out on a national level? All these people saying that THEY KNOW the status of the President’s memory. I don’t. I can’t judge it from a debate. And frankly, if we are going to do a psychiatric evaluation of one, I think we have to do BOTH. Stop following stupid rumors. Why not require a neuropsychiatric evaluation on every candidate for President and Senate and House of Representatives and the Supreme Court. And make them public. That would cause some chaos, wouldn’t it? And how do you decide who is “sane” enough to govern?

I think that gossip and triangulation is a dysfunctional form of intimacy. People feel closer when someone is whispering a secret to them. I don’t think it’s healthy. It might be normal for our culture, though. Normal does not mean healthy, after all. What do you think?

This election is like a bad hallucination. Why do we accept candidates that behave badly? Are we so addicted to television and movie drama that we want it to happen in our government? I don’t. How about you?

For the Ragtag Daily Prompt: hallucination.

Spirit take flight

Death from memory loss is a mixed bag for families.

In the past, the average time to death from Alzheimer’s was 8 years. I don’t find a number on the CDC website, CDC Alzheimer’s. I find these statistics:

  • Alzheimer’s disease is one of the top 10 leading causes of death in the United States.2
  • The 6th leading cause of death among US adults.
  • The 5th leading cause of death among adults aged 65 years or older.3

The site also says that the number of people with Alzheimer’s doubles every five years after age 65. Sigh. Those numbers are the same ones that they taught me years ago, in a different format. 6% at age 60, then 2% more every year. By 70, 26%, by 80, 46%, by 90 66%. Like hypertension, if you live long enough, you may well get it. And yet, I have had patients over 100 years old with intact memories.

The death of a family member with memory loss can have complicated grief. On the one hand, loss and grief. On the other, a burden is lifted. If the person is in memory care, the cost may be very heavy. In our town, the memory care facility costs $7000 per month. That is a heavy burden to carry when the person no longer recognizes the family or speaks. The family may feel hugely relieved when their person passes and at the same time, feel guilty. This is someone that they love and loved. And yet, they are relieved by death. I think of it as a patient of mine described it: “The grief group at the hospital said that my husband isn’t gone. I said, yes he is, he just left his body.” It is very very hard for a family to watch their loved one deteriorate, lose skills, become confused and/or frightened and/or paranoid and the process can happen for years. With an average death at 8 years, some people live beyond 8. Maybe 12 years. It is very hard.

Blessings on those who care for the memory loss people and the families who do their best for them. Alzheimer’s is one sort of dementia, but we now have many. Pick’s disease, frontotemporal dementia, Parkinson’s dementia, multi stroke dementia, alcohol induced dementia, illegal drug dementia, primary progressive supranuclear palsy, and others.

The spirit has already taken wing and let the body follow.

For the Ragtag Daily Prompt: wing.

My son took the photograph while he was visiting.

Here is the top ten causes of death in 2022: https://www.cdc.gov/nchs/data/databriefs/db492.pdf.

Age-defying

I get lots of quasi and fringe medical emails. I subscribe to some so that I know what they are “pushing”. The current trend is online “classes” where you sign up and then they have hours of talk and interviews and stuff. The talks can be three hours or more for a week. I am offered a bargain daily to sign up to be able to access the talks over and over. Hmmm, not today, thanks. I have very low tolerance for videos and television.

Currently I’m getting notes from an “age-defying” one.

I am skeptical about “age-defying” as they are describing it. However, there is a study that I think is very convincing about how to stay healthy as you get older. It was done in England. They looked at five habits: excess alcohol (averaging more than two drinks a day), inactivity (couch potato), addictive drugs, obesity and tobacco.

They had people who had none of the five, people who had all of them and people who had one or two or more. The conclusion was that for each one added, the average lifespan dropped by about four years. That is, the people who did all five tended to die 20 years sooner on average than the ones with none of the bad habits.

Recently in the US, the news said “Gosh, it turns out that any alcohol is bad for us.” I thought, how silly, when various studies made that clear over a decade ago. There was a very nice study from Finland, with 79,000 people where they looked at alcohol and atrial fibrillation. Atrial fibrillation increases the risk of strokes. They concluded that lifetime dose of alcohol was directly related to atrial fibrillation. That is, the more you drink, the sooner your heart gets really grumpy and starts fibrillating. Alcohol is toxic to the heart, the liver, the brain. Tobacco is toxic to the lungs, the heart, the brain and everything else. The addictive drugs: well, you get the picture.

So the anti-aging prescription is pretty simple to recommend. It just is not always simple to do. That is why we still have doctors. For chronic bad habits I am part mom/cheerleader/bearleader/nag/kind helper. Here is the prescription. Feel free to send me money instead of buying that seven day set of twenty one hours of lectures:

  1. Minimal or no alcohol.
  2. No addictive drugs (that includes marijuana and THC and we have almost no studies indicating that CBD is not addictive.Remember that THC and CBD and the other 300+ cannabinoids produced by the marijuana plant were not studied because it is illegal at the federal level.)
  3. No tobacco.
  4. Exercise every day: a walk is fine.
  5. Maintain your weight, which means as you get older you either have to exercise more or eat less or both. Muscle mass decreases with age.

The last anti-aging piece is some luck. Born into a war zone? Caught in a disaster, flood, fire, tsunami? Born into a family with trauma and addiction and few resources? Huge stress in your life? Discrimination or abuse? If you have had none of these, help someone else, because you have the luck. Pass it on.

The header photograph is all family members: two are my aunts and one is a cousin of my father’s and they all play church organ! Music sustains that side of the family. I took that in 2017 in Baltimore, Maryland. We had the uncles along too!

This is my grandmother on my mother’s side. I took this in the early 1980s at Lake Matinenda.

I will try to dig up the links to the two studies.

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/

adult doll house

When mom leaves in the car with the kids, dad gets trashed on beer and destroys the living room. Yes, there is an enormous black panther in the background. Will it eat dad? Maybe it will wait until some of the alcohol wears off. He won’t taste as good drunk.

_______________________________

For the Ragtag Daily Prompt: Tiger.