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

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.

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

Atypical antipsychotics - Mechanism - Effects

Anti-psychotics that are specific to a receptor subtype Effects - Reduces schizophrenic psychosis - Does not have extrapyramidal side effects

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

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]

Drugs on the brain Flashcards by aderonke adesanoye

Dopaminergic systems

Neuronal projections from the midbrain into the forebrain.

Originations

Substantial nigra
Ventral tegmental area

3 systems:

Nigrostriatal
Mesolimbic
Mesocortical
Tuberohypophyseal

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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

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Mesolimbic system

Dopaminergic system

Projection:
- Ventral tegmental area—> limbic system [nucleus accumbens]

Function:
- Reinforcement of certain stimuli [incl. drug abuse]

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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]

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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.

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Dysfunctions of the nigrostriatal system

Parkinson’s disease
- Destroys projection to basal ganglia

Huntington’s disease
- Destroys target neurones in the striatum

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Drugs used to treat Parkinson’s

- SYSTEM AFFECTED

Affects nigrostriatal system

L-DOPA [dopamine precursor]

Monoamine oxidase inhibitors
[prevents DA degradation]

DA receptor agonists

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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

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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

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Typical antipsychotics

- Examples

Chlorpromazine

Haloperidol

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Atypical antipsychotics

Mechanism
Effects

Anti-psychotics that are specific to a receptor subtype

Effects

Reduces schizophrenic psychosis
Does not have extrapyramidal side effects

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Clozapine

Atypical antipsychotic

Cortical D4 receptor antagonist [mesocortical system]
- Used to treat schizophrenic psychosis

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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

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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

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GABA-alpha receptor structure

5 Subunits:

2 alpha
3 other units

Channe- ionotrophic
- Chloride

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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

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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]

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Muscimol

Direct GABA-alpha agonist

- Binds to GABA site

Bicuculline

Direct GABA-alpha antagonist

Binds to to GABA site
Use as experimental tool.

Barbituates

Drug type
Mechanism
Uses

Indirect GABA-alpha agonist

Increases the duration at which Cl- channel opens
Combination with alcohol is fatal

Use:

Anaesthetics
Epilepsy

Alcohol

GABA-alpha agonist

Also interacts with other receptors

NMDA
Glycine
Nicotinic
Serotinin

Inverse agonists of GABA-alpha

Bind to benzodiazapine site
- Have opposite effects of benzodiazepine

Effects

Anxiety
Predispositions to convulsions

Benzodiazepine effects + uses

Decreased anxiety
Amnesia
Sedation
Muscle relaxant
Reduced convulsions

GABA-beta receptor

Structure
Function

Metabotrophic receptor- G protein

Gi= inhibitory of adenylyl cyclase
G[beta-gamma]= increased K+ conductance and decreased Ca2+ conductance.

Effects:
- Late IPSP

Inhibition
- Does not have same anti-seizure properties like GABA-alpha

Baclofen - Drug type - Effect - Uses

GABA-beta agonist - Muscle relaxant Use: - Reduced spasticity in Huntington's disease

Noradrenaline system - Projection - Function

Projections - From locus coeruleus to everywhere in the brain Function - Arousal + attention Receptors: - Metabotrophic

Alpha adrenergic receptors | - Alpha 1, 2

Metabotrophic receptors Alpha-1 - Gq Alpha- 2 - Gi

Beta adrenergic receptors | - Beta 1, 2,3

Metabotrophic receptors of noradrenaline system | - All Gs receptors

Adrenaline system

Projections: - Lateral tegmental area [medulla]----. thalamus and hypothalamus Acts on alpha and beta adrenergic receptors

Serotonergic system - Nuclei - Projections - Functions

Composed of 9 Raphe nuclei - In reticular formation Projections - Cerebellum + spinal cord [pain] - Ascending reticular activating system - Dorsal and medial raphe---> cortex Functions: - Mood - Sleep - Appeptite - Emotion - Pain

Serotonergic receptors

Mainly metabotrophic, one ionotropic

Fluoxetine

Also known as Prozac SSRI- selective serotonin reuptake inhibitor----> serotonergic system Function - Makes more serotonin more available Use: - Depression - Anxiety

MDMA - mechanism - system

Also known as ecstasy Mechanism: - Makes NADR and serotonin reuptake transporters run in reverse. - Blocks serotonin reuptake Affects serotonergic and noradrenergic systems

LSD

Drug that affects serotonergic system - 5HT1A receptor agonist - Works in Raphe nuclei. Effects - Hallucinogen [5HT2A receptor in prefrontal cortex] - Altered sensory perception - Dreamlike state

Cholinergic system

Releases acetylcholie Periphery - Ach release at neuromuscular junction and autonomic ganglia Brain - Basal forebrain complex - Brain stem complex

Basal forebrain complex

Part of the cholinergic system | - Innervation of hippocampus and neocortex

Brain stem complex

Part of cholinergic system - Innervation of dorsal thalamus - Telencephalon Function - Links brain stem and basal forebrain complex - Controls excitability of sensory relay neurones.

Myasthenia gravis

Autoimmune disorder of cholinergic system in the periphery - Destroys cholinergic receptors in muscle Effect - Muscle weakness - Degeneration---> loss of muscle activity

Alzheimer's disease - system - mechanism

Loss of cholinergic neurones in the basal ganglia | - Could underline memory deficits

Autosomal dominant nocturnal frontal lobe epilepsy

Branch of epilepsy with mutations in nicotinic receptor genes

Physostigmine - Mechanism - Use

Acetylcholinesterase inhibitor - Increases Ach at synapse Treatment for Alzheimer's disease

Neostigmine

Acetylcholine inhibitor - Increases Ach at synapse Used to treated Myasthenia gravis

Histaminergic system

Involves histamine release with histamine receptors - 3 G-protein coupled receptors Function - Arousal and attention - Vesitubular reactivity - Allergic responses - Brain blood flow