How drugs control the brain Flashcards
Describe the GABAergic system
Widespread distribution in brain
Inhibitory interneurons- to keep excitatory in check
synaptic inhibition tightly regulated
What are the properties of Projection neurons?
Type of interneuron
long axes
usually glutamate
cerebellar purkinje cells= GABAergic projection neuron
What are the properties of Local interneurons?
bi-tufted
contained within CNS
connect other neurons
mostly GABA
What are the properties of GABA A ionotropic receptors?
ligand gated Cl channel- hyperpolarises neuron
Fast IPSP
Mainly GABAergic interneurons
Gated by GABA binding
What are the properties of GABA B Metabatropic receptors?
GPCRs
Indirectly coupled to K or Ca channels via 2nd messengers
Slow IPSP
Both pre and post synaptic
What is Baclofen used to treat and how?
Used as a muscle relaxant to decrease spasticity in Huntington’s
What are the 2 direct agonist and antagonists of the GABA A receptor?
Muscimol: agonist
Bicuculline: antagonist
What is benzodiazapene?
An indirect agonist of the GABA A receptor.
Increases frequency of channel opening
Used as anxiolytic and hypnotic drug
decreases anxiety, causes sedation, relaxes muscles
What outcome does blocking the GABA A receptor have?
Seizures
What is Barbiturates?
Indirect agonist of GABA A receptor.
Increase duration channel opening
used in anaesthesia and epilepsy treatment
Binds at different site to benzo’s but has same effect
What is the effect of alcohol at the GABA A receptor?
Indirect agonist. Interacts with NMDA, glycine, nicotinic and serotonin receptors
low doses= mild euphoria, anxiolytic effects
high doses= incoordination and amnesia
Where do excitatory glutamate neurons act?
Primary route of sensory and motor info and relay neurons between brain areas
Where do inhibitory GABA neurons act?
As interneurons- maintaining balance between excitation and inhibition
What are the diffuse modulatory systems?
A specific population of neurons that project diffusely and modulate GABA and glutamate activity in their target areas
What are the 6 diffuse modulatory systems?
Dopaminergic Serotinergic Noradregergic Histaminergic Cholinergic Adrenergic
What are the 3 main Dopaminergic system and what is their function?
- Nigrostriatal system- (75% of brain DA) MOTOR control
- Mesocortical- behavioural effects
- Mesolimbic- innervates limbic parts
What type of receptors are dopaminergic receptors?
Metabotropic
What are the 2 subtypes of dopaminergic receptors
D1-like: D1 and D5. Gs- postsynaptic
D2-like: D2,3,4. Gi- pre and postsynaptic
Describe the dopaminergic nigrostriatal system
cell bodies in substantia nigra project into the striatum (caudate nucleus and putamen)= important parts of basal ganglia involved in movement
What disorders can dysfunction of the nigrostriatal system cause?
Parkinson’s: destruction of DA projections from SN to basal ganglia
Huntington’s: destruction of DA target neurons in striatum
What drugs can be used to treat disorders of the nigrostriatal system?
- L-dopa: passes through BBB
- MAO inhibitors: stops breakdown in synaptic cleft
- DA receptor agonists: act like DA
Describe the mesolimbic system
cell bodies in ventral tegmental area project into limbic system, nucleus accumbens.
role in reinforcement of several stimuli
What disorders can cause dysfunction of mesolimbic system?
Addictions: most drugs of abuse increase DA release in NAcc.
Short term: increase alertness and self-confidence. mimics activation of sympathetic nervous system
long term: natural rewards increase DA transmission and lead to reinforcement of associated behaviours. increase DA by cocaine shortcuts this pathway. Drug taking behaviour becomes reinforced= down regulation of endogenous DA system.
leads to craving drugs not natural rewards
Describe the mesocortical system
VTA projection to frontal cortex.
Role in functions such as working memory and planning
