How drugs control the brain COPY Flashcards
THE GABA-ERGIC SYSTEM
i) what type of neurons use GABA? what neurons does this keep in check?
ii) what does too much or too little GABA cause?
iii) how do many epilepsy treatments harness GABA transmission?
i) inhibitory interneurons - keep excitation in pyramidal neurons in check
ii) too much GABA = loss of conciousness/coma
too little GABA = convulsions and seizures
iii) epilepsy treatments act to increase GABA transmission
INHIBITORY CONTROL OF PYRAMIDAL NEURONS
i) which NT do projection neurons use?
ii) where do pyramidal cells recieve information from?
iii) which neurons filter this information
iv) which two cells control output of pyramidal cells?
v) which area of the cell is the action potential generated?
vi) label A-D
i) glutamate
ii) from excitatory Glu synapses
iii) GABAergic interneurons
iv) basket and axo-axonic cells
v) axon hillock
vi) A = glutamate synapse, B = GABAergic synapse, C = axoaxonic, D = basket cell
TWO FAMILIES OF GABA RECEPTORS
i) what type of receptor is GABAa? what ions pass through it? what neurons are they mostly found on?
ii) which type and speed of post synaptic potential do GABAa conduct?
iii) what type of receptor is GABAb? which two ion channels is it indirectly coupled to? what effect does it have on each?
iv) which type and speed of post synaptic potential does GABAb conduct? are they found pre or post synaptically?
i) GABAa = ionotropic
- ligand gated Cl- channel
- found on GABAergic interneurons
ii) conduct fast inhib PSPs
iii) GABAb is metabotrophic and is indirectly coupled to K+ and Ca2+ cannels
- opens K+ chann and closes Ca2+ channels
iv) conducts slow inhib PSPs
- found pre and post synaptically
GABAa RECEPTORS
i) what structure does it have?
ii) which ion does it flux? in which direction? how many agonist molecules need to bind to allow this?
iii) what potential is resting Cl- potential close to? what does activation/increasing chloride permeability do to the neuron?
iv) during neurological development what role does GABA play? how does this change post birth?
v) name three molecules that can also bind GABA receptors
i) heteropentameric structure (2xalpha + 3 other subunits)
ii) fluxes chloride ions (move out)
- need two agonists to bind for Cl to be fluxed
iii) Cl- potential is close to resting potential
- increasing chloride permeability hyperpolarises the neuron
iv) during development GABA is both inhib and excitatory
- post birth its only inhibitory
v) benzos, steroids and barbiturates
GABAa receptors and drugs
i) which site do direct agonists/antagonists bind? give an example of each
ii) name three indirect agonists of the GABAa receptor? what effects do these have on GABA?
iii) binding of which molecule increases receptor affinity for GABA and frequency of channel opening?
iv) what effect does barbiturates have on the channel? name two applications of these
v) name two effects of benzos
i) bind at the GABA sute (compete with GABA)
- agonist = muscimol
- antagonist = bicuculine
ii) indirect agonists enhance effects of GABA = benzodiazepenes, barbiturates and alcohol
iii) binding of benzos increases receptor affinity for GABA, inc frequency of channel opening
iv) barbiturates increase duration of channel opening
- used in anaesthesia and epilepsy treatment
v) anxiolytic and hypnotic effects
GABAa RECEPTOR - BENZODIAZEPENE ACTION
i) which subunit of the receptor do they bind? what type of agonist does this make them?
ii) what happens to the receptor on binding of a benzo? what effect does this have on GABA
iii) name four effects
iv) what type of drug will bind to the benzo site and have opposite effects?
i) bind the alpha subunit = indirect agonist
ii) binding of a benzo changes conformation of receptor so GABA activation of receptor is mor effective
iii) reduce anxiety, cause sedation, reduce convulsions, relax muscles, cause amnesia
iv) inverse agonists
GABAa RECEPTOR - BARBITURATES AND ALCOHOL
i) do barbiturates and alcohol bind at the same site?
ii) what effect do they both have? what can happen if they are used together?
iii) name four receptors alcohol also acts on
iv) name two effects of low doses of alcohol and two effects of high dose
i) no they bind at different sites on the receptor
ii) both enhance GABAa activity
- used together = can be fatal as effects are additive
iii) alcohol - NMDA, glycine, nicotinic and serotonin receptors
iv) low doses = mild euphoria and anxiolytic
high doses = incoord and amnesia
GABAb RECEPTOR
i) which G protein is it coupled to? what effect does this have on second messengers?
ii) what ion does it increase conductance of? what post synaptic potential does this produce?
iii) what is an agonist? what condition can this be used in?
iv) does inhibition of GABAb have the same effect of inhibition of GABAa?
i) coupled to Gi and inhibits adenylyl cyclase
ii) increases conductance of K+
- produces a slow hyperpolarising current > late IPSP
iii) baclofen is an agonist - can be used as a muscle relaxant in huntingtons disease
iv) no
NEUROTRANSMITTER SYSTEMS
i) which neurons are the primary route of sensory and motor information as well as relay neurons between brain areas?
ii) which NT do interneurons use? what does this allow?
iii) what neurons do the diffuse modulatory systems modulate? (2)
iv) name five types of neurons diffuse modulatory systems? where do these subpopulations arise from?
i) glutamate neurons
ii) GABA - allows balance between excitation and inhibition
iii) modulate glu and GABA neurons
iv) dopaminergic, serotonergic, cholinergic, adrenergic, histaminergic
- synth in specific populations in the brainstem and project with long axons
THE DOPAMINERGIC SYSTEM
i) where are the cell bodies of DA neurons found? which brain area do they project to?
ii) which three systems make up the DA system? which one uses the majority of the brains dopamine?
i) cell bodies in the midbrain and project to the forebrain
ii) nigrostriatal, mesolimbic and mesocortical
- nigrostriatal uses most (75%) of the brains dopamine
DOPAMINE RECEPTORS
i) which type of receptors does dopamine exclusively work through? how many are there?
ii) what types of post synaptic potential does dopamine produce? what does this depend on?
iii) which two DA receptors are excitatory? which G protein and second messengers do they stimulate?
iv) which three DA receptors are inhibitory? which G protein do they signal to? what effect does this have on K+ and Ca2+ channels?
v) what role do presynaptic autoreceptors play?
i) metabotrophic - D1-5
ii) DA can produce IPSPs and EPSPs depending on the receptor and G protein coupled to it
iii) D1 and 5 are excitatory
- stimulate Gs > adenylyl cyclase (and PLC post synaptically)
iv) D2,3,4 are inhibitory
- signal to Gi which opens K+ channels and closes Ca2+ channels
v) presynaptic autoreceptors monitor the amount of transmitter released
NIGROSTRIATAL SYSTEM
i) hwat is this system prinicpally involved in?
ii) where do cell bodies sit? which structure do they project to?
iii) name two diseases dysfunction in this system can cause? what type of DA projections/neurons are damaged in each?
iv) name three drug treatments that can correct dysfunction and how each one works
i) movement
ii) cell bodies sit in the substantia nigra and project to the striatum
iii) parkinsons - destruction of DA projections from SN to basal ganglia
huntingtons - destruction of DA target neurons in the striatum
iv) LDOPA - passes BBB and is converted to DA
- MAO inhibitors - stops breakdown of DA in the synaptic cleft
- DA agonists - ehnance DA receptors (PD treatment)
MESOLIMBIC SYSTEM
i) where do cell bodies sit? and which two areas do they project to?
ii) what role does this system play?
iii) what happens in dysfunction of the system? what happens in the nucleus accumbens?
iv) what type of drugs are cocaine and amphetamine? name three immediate effects
v) what can large doses cause? what do periphearal effects mimic? give an example
vi) name three long term effects
i) cell bodies in ventral tegmental area and project to the limbic system
ii) role in reinforcement and reward (inc drugs of abuse)
iii) dysfunction = addiction
- can lead to enhanced DA release from teh NAcc
iv) cocaine and amphet are psychomotor stimulants
- increased alertness, confience, decreased appetite
v) large doses can cause sterotypy and psychosis
- peripheral effects mimic activation of the symp nernous system eg inc heart rate
vi) long term effects = reinforce cocaine behaviours and less interest in natural reward, downreg of endog DA system = craving
MESOCORTICAL SYSTEM
i) name two things it plays a role in?
ii) where do cell bodies sit? where do they project to?
iii) what disease arises in dysfunction? name three characteristic signs of this
iv) name two drug classes that act on this system
i) role in working memory and planning
ii) cell bodies in ventral tegmental area and project to the prefrontal cortex
iii) dysfunction = schizophrenia (poor working memory/planning and organisation)
iv) typical and atypical antipsychotics
TYPICAL AND ATYPICAL ANTIPSYCHOTICS
i) give an example of each
ii) what action do typicals have at DA receptors? what does this do to the DA turnover? what effect do they have on post synaptic receptors?
iii) which DA system do they work on?
iv) name two side effects of typical APs
v) how are atypical APs different to typical? name two negative effects they can reduce
i) typical = haloperidol, atypical = clozapine
ii) typical are DA receptor antagonists (pre and post syn)
- increase DA turnover > loss of autoreceptor inhib on presyn
- block post synaptic receptors > upregulation
iii) work on the mesocortical system
iv) typical APs > action on other DA systems eg nigrostriatal
- extra pyramidal SEs eg tardive dyskinesia
- supersensitivity of receptors due to blockade
v) atypical are specific to DA receptor subtypes
- can reduce psychosis and no EPs
SEROTONIN RECEPTORS
i) what are the two classes of 5HT receptors?
ii) how are the receptors expressed across the brain? what does this allow?
iii) which channel fluxes Na, K and Ca? is this excitatory or inhibitory?
i) metabotropic and ionotropic
ii) differentially expressed across many brain areas to allow 5HT to have lots of functions
iii) 5HT3 receptor fluxes Na, K and Ca = excitatory
