Psychomimetics Flashcards by Lara Smelly

Whats MFB?

Mesolimbic system (collection of dopaminergic neurons that project from ventral tegmental area to the nucleus accumbens)

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What active constituent does peyote contain?

Mescaline

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Effects of PCP?

-altered body image
-cognitive disorganisation
-drowsiness and apathy
-feeling of isolation
-hypnagogic (dreamlike) states
-euphorian and inebriation

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What does PCP stand for?

Phenylcyclidine

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What two main classes of receptors does PCP interact with?

1) sigma opiate receptor - modulates NAdr
2) Glutamate receptor

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How does PCP interact with Glutamate receptors?

Non-competitive antagonist of the NMDA receptor

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What is NMDA?

N-methyl D-aspartate is a ligand gated ion channel (non-selective cation channel)

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What does PCP cause an increase in?

An increase in subcortical VTA dopaminergic activity

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Where is NMDA expressed?

GABA neurons in the subcortical regions

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What does PCP do?

PCP removes cortical inhibition

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How does cocaine act?

Acts by blocking the reuptake of catecholamines into the presynaptic terminal causing an increase in the concentration of catecholamines in the synaptic cleft

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What happens in increased levels of cocaine use?

Can elicit tremors, convulsions and CNS depression

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Name three actions of cocaine?

1) Local anaesthetic (blocks voltage-gated Na channels)
2) Causes euphoria
3) Appetite suppressant

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Name three actions of cocaine?

1) Local anaesthetic (blocks voltage-gated Na channels)
2) Causes euphoria
3) Appetite suppressant

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Name some actions of amphetamines?

raises blood pressure
appetite suppressant
causes euphoria

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Uses for amphetamines (AMPH)

weight loss
narcolepsy
attention deficit disorder (ADD)

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Name drugs that can trigger/ cause psychosis

amphetamine, PCP, cocaine

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How does AMPH act?

AMPH binds to the DA transporter and reverses the pump on the presynaptic terminal pumping DA out into the synaptic cleft and pumping AMPH into the presynaptic terminal

what does MDMA stand for?

3,4-methylenedioxy-N-methylamphetamine

What is MDMA’s mechanism of action?

It acts on 5-HT receptors and effects catecholamine transmission.
- increases 5-Ht concentration by reducing 5-HT reuptake
- it blocks MAO stopping the metabolisation of monoamine neurotransmitters (dopamine, serotonin etc.)

What is addiction?

When a physical and psychological dependance can occur

Name three features of addiction

Compulsion to take the drug
‘Withdrawal’ syndrome
Tolerance

What is tolerance ?

A decreased response to repeated administration

What is ‘withdrawal’ syndrome?

When opposite effects to those experienced in the presence of the drug due to circuits adapting to the drug’s interaction and highlights the plasticity of the brain

Example of a withdrawal ?

Heroin causes constipation so a withdrawal symptom is diarrhea

What is the dopamine pathway in the brain?

MFB (mesolimic pathway)

what animal model can show DA's involvement with cocaine?

'knock out' experiment - cocaine administered produced no change in base-line DA (NO INCREASE in locomotor activity) - Animals will self-administer cocaine meaning theres another 'reinforcing stimulus' other than DA

What is F105 in DA transporters?

F105 is a phenylalanine residue which allows fo high affinity cocaine binding

What would happen if there was a mutation in F105 of DA transporter

cocaine can no longer bind

name the four drugs that act on the VTA

ethanol nicotine opiates THC

name the four drugs that act on the nucleus accumbens

cocaine amphetamines opiates THC

where does nicotine act directly and indirectly?

- acts directly on DA - acts indirectly on glutamate (signalling onto DA neurons)

what is the percentage chance genetically of inheriting addiction?

30-60%

what is the orbitalfrontal cortex involved in?

descision making and controlled behaviour

if someone suffers from addiction what would an image of the orbitalfronta cortex show?

decreased activity to someone not addicted

what is 18F- Fluoromethylspiroperidol used for in a PET scan?

labels dopamine (D2) receptors in the brain

what would be expected to be seen in a PET scan of a cocaine abuser if 18F is present?

low levels of D2 receptors

why does cocaine abuse lead to decrease in D2 receptors?

Downregulation of D2 receptors (homeostatic adaptation)

what is a long term side effect of cocaine abuse?

changes in gene expression via increase in DA leading to increase in cAMP therefore CREB and immediate early gene expression - altering levels of receptor expression

what does ethanol cause in the mesolimbic pathway?

increase in DA

what variations of genes are associated with addiction?

ALDH2 D2 OPRM1

what is ALDH2 gene responsible for?

metabolising alcohol - catalyses the breakdown of aldehyde acetic acid

name and describe a sympathomimetic amine

Amphetamine a stimulant which mimics the effects of endogenous agonists of the sympathetic nervous system

describe AMPH mechanism of action

extracellular binding to DA transporter = transporter to be reversed and pump out DA and pump AMPH into the presynap terminal = increase in conc of DA in synaptic cleft