T1L13 how drugs control the brain Flashcards
the GABAergic system
- widespread throughout brain
- inhibitory neurons- keep excitation under control
too much GABA = loss of consciousness and coma
too little GABA = convulsions and seizures
2 main families of GABA receptor
- GABAa ionotropic recepors
- ligand gated cl- channels
- fast IPSPs (inhibitory postsynaptic potentials)
- mainly GABAergic neurons - GABAb metabotropic receptors
- g protein coupled receptors
- indirectly coupled to k+ or Ca2+ channel through 2ndry messengers
- slow IPSPs
- both pre and postsynaptic
GABAa receptors
and drugs
- 2 alpha and 3 more subunits
- pentamer
- cl- channel gated by binding of 2 agonist molecules
- cl- potential is near resting potential, increasing cl- permeability. this hyperpolarises the neuron
- this hyperpolarisation decreases the depolarising effects of excitatory input
drugs:
muscimol - agonist (direct)
bicucilline - antagonist (direct)
benzodiazepine - binding increases receptor affinity for GABA, leading to increase frequency of channel opening. anxiolytic and hypnotic properties. (indirect)
barbiturates- increase duration of channel opening - used in epilepsy (indirect)
alcohol - agonist (indirect)
benzodiazepine
eg Valium - acts on GABAa receptor - indirect anagonist - binds to alpha subunit changing the receptor conformation to be more effective. effects: reduced anxiety sedation muscle relaxant amnesia
barbiturates and alcohol
- bind at different sites on receptor
- both enhance GABAa activity
GABAb receptor
- metabotrophic
agonist - baclofen (used as muscle relaxant eg in huntingtons)
Gi coupled- inhibits adenylyl cyclase Gby gated K+ channel: - increase k conductance - decrease ca2 conductance this slows the hyperpolarising current (late inhibitory postsynaptic potential)
inhibition of GABAb transmission has different behavioural effects compared to GABAa receptors
neurotransmitter systems list: diffuse modulatory systems
main workhorse: GABA and glutamate
Glutamate neurons - primary route of sensory and motor information and relay neurons between brain areas
GABA neurons - interneurons, maintain balance between excitation and inhibition
diffuse modulatory systems: dopaminergic (A) serotonerg9achic (5-HT) noradrenergic (NA/NE) adrenergic cholinergic (ACh) histaminergic
diffuse modulatory systems def
Specific populations of neurons that project diffusely and modulate the activity of Glutamate and GABA neurons in their target areas.
eg serotonergic, noradrenergic
the dopaminergic system
and the other baby systems
this one is fucking bleak I am so sorry I have to learn this
dopamine neurons:
- cell bodies in midbrain
- project into forebrain
dopamine receptors:
metabotropic receptors D1-D5
- dopamine produces both epsp and ipsp depending on receptor subtype and the coupled g proteins
D1-like (1&5) - Gs
- stimulate adenylyl cyclase
- stimulate phospholipase c
- postsynaptic
D2-like (2,3,4) - Gi
- inhibit adenylyl cyclase
- open K+ channel
- close ca2+ channel
- postsynaptic and (presynaptic autoreceptors)
the balance of these 2 maintains the dopaminergic tone
nigrostriatal system- cell bodies in substantia nigra project to the striatum (caudate nucleus and putamen)
- important part of basal ganglia for movement
- dysfunction is Parkinson’s disease
drugs: eg dopamine receptor agonists treat parkinsons
mesolimbic system- cell bodies in VTA project to the limbic system and nucleus accumbens (NAcc)
- role of reinforcement (reward) to several stimuli, including drugs of abuse
- dysfunction as addictive drugs of abuse lead to increased DA release in NAcc
eg cocaine and amphetamine
look at this s20
mesocortical system- VTA projections into prefrontal cortex
- role in working memory and planning
dysfunction: schizophrenia
drugs:
antipsychotics eg chlorpromazine
- DA receptor antagonists
- increase DA turnover > lose autoreceptors inhibition
- blockade of postsynaptic receptors > upregulation
the serotonergic system
this ones a bit nicer eh
consists of 9 raphe nuclei in reticular formation with diffuse projections (each to a different part of brain)
- descending projections into cerebellum and spinal chord
- dorsal and medial raphe project through the cerebral cortex.
raphe neurons fire tonically during wakefulness and stop during sleep
metabotropic and ionotropic receptors
serotoninergic system effects:
- mood
- sleep
- pain
- emotion
- appetite
drugs:
SSRIs eg fluoxetine (Prozac)
MDMA- blocked reuptake and reversed transporters
drugs with effects on serotonergic receptors:
- LSD - agonist at 5HT1A
the noradrenergic system
projections from the locus coeruleus throughout brain
- role in arousal and attention
- metabotropic receptors
alpha adrenergic receptors:
a1 > Gq
a2 > Gi
beta adrenergic receptors:
b1, b2 and b3 > Gs
the adrenergic system
primarily in lateral tegmental area, projecting into thalamus and hypothalamus
- acts on a and b adrenergic receptors
the cholinergic system
in the periphery: at NMJ and synapses in autonomic ganglia
in the brain:
- basal forebrain complex
- cholinergic innervation of hippocampus and neocortex - brain stem complex
- innervates the dorsal thalamus and telencephalon (control eexcitability of sensory relay neurons and provide a cholinergic link between the brain stem and basal forebrain complex)
see pic s30
disorders:
peripheral - myasthenia gravis (autoimmune destruction of cholinergic receptors, muscle weakness, loss of muscle activity)
brain- Alzheimer’s (loss of cholinergic neurons in basal ganglia- possibly underlies deficits in memory associated with disease)
addiction- nicotine
epilepsy
- ADNFLE epilepsy associated with mutations in nicotinic receptor genes
acetylcholinesterase inhibitors:
- prolong action of acetylcholine at synapse
- treatment for alzheimers disease and masthenia gravis
botox- prevents release of ach at nmj
2 types of acetylcholine receptor
muscarinic- metabotropic
nicotinic- ionotropic
muscarinic receptors
- for acetylcholine
- metabotropic
lead to hyperpolarisation or depolarization by opening or closing of k+, cl-, ca2+
pre and post synaptic
presynaptic»_space; -ve feedback»_space; stop ach release
