lec 8, stimulants and alcohol

How long does cocaine take to peak in blood

30-60 min, it is lipholic and easily penetrates blood-brain barrier

Half life of cocaine

Relatively quick, 30-90 mins

Cocaine is a stimulant, it increases:

Euphoria, energy, confidence, activity, alertness, attention

Cocaine works at ..

Mono-aminergic synapses

Any synapse that use Monoamine as the neurotransmitter

What is a reuptake channel

A way for the presynaptic terminal to recycle neurotransmitter from the synaptic cleft back into the presynaptic terminal, ready to be packaged into vesicles again

Consequences of reuptake channels

Reduces neurotransmitter in synaptic cleft because it clears it, stopping neurotransmission by re absorbing Neurotransmitter into presynaptic cleft

Recycles and reuses so doesnt have to make nt from scratch every time

What does cocaine have to do with the reuptake channels

Cocaine blocks these reuptake channels. Nt doesn’t get recycled back into presynaptic terminal, stays in synaptic cleft for longer at higher concentration.

Cocaine doesn’t release Monoamines (serotonin, dopamine, noradrenaline), but keeps it in synapse for longer meaning its effect lasts longer

What does activity at noradrenergic synapse suppress

Arousal and plateau - noradrenergic synapses are used by the sympathetic nervous system, when noradrenaline is released by sympathetic nervous system it will narrow the blood vessels, then they can’t be dilated so blood can’t flow into cavities of genitals so arousal would not work

Long term effects of cocaine

blocking reuptake so not recycling monoamines - they will have less nt in them, causing lower levels so ‘crash’ into depression

Remedied by taking more cocaine - binges

Sz - like symptoms e.g. hallucinations, mood disturbances, repetitive behaviours etc

Destruction of nasal septum - no blood/oxygen etc

Addictiveness of cocaine

Cocaine works on dopaminergic synapses - one of the main ones is from VTA to N. Accumbens (mesotelencephalic system).

If vta fires APs and releases dopamine - cocaine makes dopamine stay in synapse for longer so it is interpreted as lots of dopamine being released - which says do this behaviour again

What do amphetamines work on

Same synapses as cocaine (mono-aminergic) also same reuptake channels as cocaine

What do most amphetamines do to the reuptake channels

Instead of blocking reuptake channels, they reverse them

They push neurotransmitter out through reuptake channels, so dont need APs to release neurotransmitter

Some amphetamines like Ritalin act similarly to cocaine by blocking reuptake , the release is much more gradual and doesn’t have same efffects as cocaine - effective treatment for ADHD

Caffeine

Concentration peaks after approx 40 mins, easily passes blood brain barrier - biological half life of 3.5-5 hrs

Caffeine is a psychostimulant so ..

Increases alertness, induces clear thinking and restlessness, difficulty with fine movements, increases cardiac contractions and constricts blood vessels

What receptors does caffeine block

adenosine receptors

What is adenosine

adenosine is involved in sleep induction and vasodilation (signalling in blood vessels - makes expand)

Stimulates adrenaline release from adrenal medulla

Withdrawal symptoms of caffeine

Headaches

Sleepiness

Irritability

Difficulty concentrating

Nicotine

Smoked or vaped typically, comes from tobacco leaf

Within 7 sec of a puff, 25% of the nicotine has already crossed the blood-brain barrier

Nicotine short term effects

Induces vomiting, relaxes muscle tone, reduces weight gain, increases heart rate and blood pressure

Physiological action of nicotine?

Binds to nicotinic acetylcholine receptors

Nicotine is an agonist at these receptors

Nicotine receptors are involved in stimulation of sympathetic nervous system including release of adrenaline from adrenal gland

Nicotinic receptors are also found in brain

Nicotine stimulates both systems parasympathetic and sympathetic but they have opposite effects.

However sympathetic outweighs – meaning higher alert, suppression of appetite, more alert.

Nicotine long term effects

Body develops tolerance

Wears heart out more quickly

Major problems are from other components of tobacco and cigarette smoke which can cause cancer, cardiovascular disease etc

Nicotine with dopamine and N.Accumbens

Very strong dopamine release in the nucleus Accumbens from the nicotine being injected

Addiction in rats with nicotine and cocaine

harder to get rats trained to self administer nicotine than cocaine

Alcohol

Reaches max blood concentration in 30-90 mins

Easily crosses blood brain barrier - soluble in water and lipids

Eliminated through liver mostly which breaks it down at a steady rate

Short term effects of alcohol

Mild euphoria, lowers anxiety, slower reflexes, memory problems, sedation etc

Dilation of blood vessels (heat loss, can’t feel cold)

Diuretic (more urination)

Physiological action of alcohol

1. Agonist of GABA-A receptors (mimic/increase effect of gaba) - increasing inhibitory processes

2. Antagonist of NMDA receptors (suppresses excitatory processes) NDMA involved in memory formation in hippocampus

Alcohol long term effects

cirrhosis of the liver - liver failure

Brain damage - Korsakoff’s syndrome

Foetal alcohol syndrome if pregnant

Physical addictiveness of alcohol

Hangover - mild withdrawal

Delirium tremens - strong withdrawal

Psychological dependence of alcohol

Increases dopamine in n.accumbens

Strong heritable component to alcoholism