6. Neurotransmission and drug abuse PDF

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Summary

AddictionDefinition of addiction (Orfort (1985) “Loss of control over a form of behavior pleasurable to most people” Something that used to brighten the day, now is as necessary as air and water. (Liking vs needing) Recreational drugsNicotineInteracts with one of the two subtypes of acetylcholine re...

Description

Addiction Definition of addiction (Orfort (1985) -

“Loss of control over a form of behavior pleasurable to most people” -

Something that used to brighten the day, now is as necessary as air and water. (Liking vs needing)

Recreational drugs Nicotine Interacts with one of the two subtypes of acetylcholine receptor (nicotine receptor) -

Is a selective compound that only binds with the nicotinic receptor. (the other one is called muscarinic receptor binds to muscarinic from mushrooms)

Alcohol, Modulated the GABAA and GABAB receptor, also noradrenalin and opioid receptors

Opiates and heroin Interact with a specific receptor called the Opioid peptide receptor -

The brain produces these opioid peptides naturally (aka Opioid miu) -

used for the modulation of pain

MMDA (ecstasy) Serotonin 2A receptor and serotonin transporter

Cocaine (psychostimulants) Blocks of Dopamine transporter -

Transporter = same as reuptake pump

Made from coca shrub leaves in south america -

History of coke -

Block the dopamine transporter (Transporter = inactivates the dopamine after a certain point to return it to presynaptic axon terminal)

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Coke was also a local anaesthetic (resembling Lidocaine)

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This makes the dopamine stay longer in the synapse to increase likelihood of it binding with receptors in the post synaptic cleft.

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This however does not depend on the blocking of the dopamine transporter. -> Coke at higher levels blocks sodium channels (low depolarisation, low action potentials fired)

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BIO

1. Dopamine is released into the synaptic cleft (after the presynaptic depolarisation) 2. It acts on the postsynapse 3. It is taken back up by the dopamine transporter (DAT) 4. It is incorporated into the vesicles by the vesicular monoamine transporter (VMAT -

Blocks the DAT

PET imaging Cocain users shown neutral image and cocaine related images. -

> activation is shown in the prefrontal cortex, the medial temporal cortex (lateral prefrontal areas) and ventral striatum and other basal ganglia structures.

Imaging study Showed an image thats ‘funny’ and one that isn't. -

The funny pic caused -

Activation of ventral striatum (part of the mesolimbic dopamine system)

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Motor activation (a chuckle)

Amphetamine Releases dopamine -

manmade , created it 1887

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Have clinical uses for ADHD etc

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Psychotropic effects (at higher doses ) -> used in WW2 to occupy troops as they waited -

Also as a nasal decongestant until recently (1900’s) Amphetamine is transported into the presynaptic terminal where it displaces dopamine from the vesicles leading to its synaptic release. (pops the bubble)

Barbiturates Modulates GABAA receptor

Cannabis Cannabinoid CB1 receptor -> the brain produces endogenous compounds that interact with these receptors -

THC = major psychoactive component (exogenous compound, something the body takes in from the outside)

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Cannabidiol =

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Cannabigerol

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Endogenous (something the body produces itself) neurotransmitters : Anandamide, 2-arachidonoylglycerol (2-AG)

Synthetic cannabinoids John huffman -

Crated drugs that mimicked neurotransmitters that have high efficacy (how well it binds to the receptor) and high affinity (how well can it imitate the neurotransmitter)

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9-THC has high affinity but lower efficacy

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Full agonist

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Partial agonist

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Produces high efficacy and affinity (at a high dose) Produces a smaller effect than a full agonist (at a high dose) -> moderate affinity, high efficacy

Antagonist -

Produces negligible effect (at a high dose) -> reduces the effect of partial and full agonist. (connects to the receptor but no replication. Competes w/ agonists to bind w/ receptor thus lowering their effect)

Dopamine and Brain reward circuit Jim owes Can be made from natural and pharmaceutical ways -

Ventral tegmental area (VTA) -

Dopamine cells sit here

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Their axons connect up till the (acc)

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The ventral striatum also known as the nucleus accumbens (Acc)

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GABA circuit -

The return circuit goes from the Acc back to the VTA

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Jim accidentally stimulated the circuit of a rat brain and the rat came back to the place over and stimulation had occurred. -> proved the circuit existed

over where the

Most drugs interact with these dopemnergic circuits

Tolerance : -

In order to get the specific effect from the drug, with repeated doses, you have to take more of that drug.

Withdrawal -

If you don't have the the drug, u crave it hard core

Drugs have side effects that range from good to bad Ex: methamphetamines cause somato-sensory hallucination which are a common side-effect. (Feels like bigs crawling under the skin)

Place preference task -

2 types of mice -

Normal mice (wild type) and mice which are genetically modified to not have miu opioid receptors.

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both mice are given opioids in one place and saline solution in the other

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Eventually, the normal mice starts roaming around the place which gave them opioids

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The genetically modified mice didn’t give a shit and about where to roam because opioids didn't have an influence on them.

Treating drug addiction 1. Substitute the drug with one that has less rewarding properties a. Heroin -> methadone 2. Block the rewards the rewarding drug by treating with an antagonist. a. Antagonist may cause heavy withdrawal (ex: Naloxone or naltrexone) i.

Naltrexone may help to reduce heavy drinking

b. Partial antagonist (buprenorphine) for really addicted patients of heroine

3....