Psychomimetics Flashcards
Whats MFB?
Mesolimbic system (collection of dopaminergic neurons that project from ventral tegmental area to the nucleus accumbens)
What active constituent does peyote contain?
Mescaline
Effects of PCP?
-altered body image
-cognitive disorganisation
-drowsiness and apathy
-feeling of isolation
-hypnagogic (dreamlike) states
-euphorian and inebriation
What does PCP stand for?
Phenylcyclidine
What two main classes of receptors does PCP interact with?
1) sigma opiate receptor - modulates NAdr
2) Glutamate receptor
How does PCP interact with Glutamate receptors?
Non-competitive antagonist of the NMDA receptor
What is NMDA?
N-methyl D-aspartate is a ligand gated ion channel (non-selective cation channel)
What does PCP cause an increase in?
An increase in subcortical VTA dopaminergic activity
Where is NMDA expressed?
GABA neurons in the subcortical regions
What does PCP do?
PCP removes cortical inhibition
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
What happens in increased levels of cocaine use?
Can elicit tremors, convulsions and CNS depression
Name three actions of cocaine?
1) Local anaesthetic (blocks voltage-gated Na channels)
2) Causes euphoria
3) Appetite suppressant
Name three actions of cocaine?
1) Local anaesthetic (blocks voltage-gated Na channels)
2) Causes euphoria
3) Appetite suppressant
Name some actions of amphetamines?
- raises blood pressure
- appetite suppressant
- causes euphoria
Uses for amphetamines (AMPH)
- weight loss
- narcolepsy
- attention deficit disorder (ADD)
Name drugs that can trigger/ cause psychosis
amphetamine, PCP, cocaine
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
