Drugs on the brain Flashcards
Dopaminergic systems
Neuronal projections from the midbrain into the forebrain.
Originations
- Substantial nigra
- Ventral tegmental area
3 systems:
- Nigrostriatal
- Mesolimbic
- Mesocortical
- Tuberohypophyseal
Nigrostriatal system
- Function
- Projections
Dopaminergic system–> produces 75% of dopamine in the brain.
Projection:
- Cell body in substantial nigra
- Neurones project into the striatum [caudate nucleus and putamen]
Function:
- Motor—.> voluntary movement
Mesolimbic system
Dopaminergic system
Projection:
- Ventral tegmental area—> limbic system [nucleus accumbens]
Function:
- Reinforcement of certain stimuli [incl. drug abuse]
Addicition
Dysfunction of the mesolimbic system [responsible for reinforcement]
Drug abuse enchances dopamine release in the nucleus accumbens of the limbic system/
Also dysfunction of the cholinergic system [nicotine]
Cocaine and amphetamine
- System affected
- Immediate and long-term effects
Affects the dopaminergic, mesolimbic system.
Immediate effects:
- Increased alertness, self confidence
- Europhia
- Decreased appepties
- Large dose= psychosis and stereotypy
- Can mimic SNS activation
Long term:
- Natural rewards increase dopamine transmission
- Down-regulation of DA system= craving
- Drug-taking behaviour reinforced.
Dysfunctions of the nigrostriatal system
Parkinson’s disease
- Destroys projection to basal ganglia
Huntington’s disease
- Destroys target neurones in the striatum
Drugs used to treat Parkinson’s
- SYSTEM AFFECTED
Affects nigrostriatal system
L-DOPA [dopamine precursor]
Monoamine oxidase inhibitors
[prevents DA degradation]
DA receptor agonists
Mesocortical system
- Projections
- Function
- Dysfunction
Dopaminergic system
- Projections from the ventral tegmental area to the prefrontal cortex
Function:
- Influences personality, planning and working memory
Dysfunction:
- Schizophrenia
Typical antipsychotics
- Mechanism
- Effects [system affected]
Dopamine receptor antagonists
- Increases dopamine turnover
- Up-regulation [blocks postsynaptic receptors]
- Loss of auto regulation inhibition [blocks pre-synaptic receptors]
Effects
- Antipsychotic effects by influencing the mesocortical system
- Extrapyramidal side effects
Typical antipsychotics
- Examples
Chlorpromazine
Haloperidol
Atypical antipsychotics
- Mechanism
- Effects
Anti-psychotics that are specific to a receptor subtype
Effects
- Reduces schizophrenic psychosis
- Does not have extrapyramidal side effects
Clozapine
Atypical antipsychotic
Cortical D4 receptor antagonist [mesocortical system]
- Used to treat schizophrenic psychosis
Extrapyramidal side effects of typical antipsychotics
Set of symptoms that arise from the chronic blockade of dopamine receptors
- Makes the mesocortical system hypersensitive
Symptoms:
- Tardive dyskinesia
- Parkinsonism
Inhibitory control of cortical pyramidal neurones
- Cells
- Function
Dendrite targeting cells:
- GABAergic interneurones
- Controls input by impinging the dendrites at different sites.
Basket and axo-axonic cells
- GABAergic interneurones that control outputs
- Basket= soma
- Axo-axonic—> on axon. Greatest influence on AP generation
GABA-alpha receptor structure
5 Subunits:
- 2 alpha
- 3 other units
Channe- ionotrophic
- Chloride
Mechanism of GABA-alpha receptor
Gated by two agonists
- GABA
- Another agonist [i.e benzodiazapine]
Binding of two agonists increases chloride permeability
- Hyperpolarises plasma membrane [Cl- enters cell]
- Decreases excitability of cell
Benzodiazapine
- Drug type
- Mechanism
- Effects
Indirect GABA-alpha agonist
- Binds to alpha subunit
- Increases receptor affinity for GABA
Effects- rapid onset
- Increases frequency of Cl- channel opening
- Rapid onset of Anxiolytic and hypnotic effects [less effective long term]
