Understanding drug action in the central nervous system

How do drugs affect neurotransmission in the CNS?

Drugs can enhance or inhibit neurotransmission by affecting neurotransmitter release, receptor binding, or reuptake.

How does increased dopamine in the associative striatum affect the brain?

It can lead to psychotic symptoms.

What is the mechanism of current antipsychotic drugs?

They act as dopamine receptor antagonists to reduce dopamine overactivity.

What do dopamine agonists do?

They increase dopamine neurotransmission, which can induce psychotic symptoms

What is the prevalence of schizophrenia?

affects 0.3-0.7% of the population, with earlier onset in men (late teens to early 20s) than women (mid-20s to early 30s).

How is schizophrenia diagnosed (DSM-5 criteria)?

Requires two or more symptoms (e.g., delusions, hallucinations, disorganized speech) persisting for six months with functional impairment.

What are the risk factors for schizophrenia?

• Genetic: 10% risk if a first-degree relative is affected.

• Environmental: Prenatal factors, stress, drug use (especially cannabis), social adversity.

What are the main theories of schizophrenia?

• Dopamine Hypothesis: Excess dopamine causes positive symptoms.

• Glutamate Hypothesis: Glutamate dysfunction contributes to negative and cognitive symptoms.

What are the symptoms of schizophrenia?

• Positive: Hallucinations, delusions, disorganized speech.

• Negative: Lack of motivation, reduced speech, emotional blunting.

• Cognitive: Impaired memory, concentration, problem-solving

How do antipsychotic drugs work?

They block dopamine D2 receptors, reducing psychotic symptoms.

What is a major side effect of D2 receptor blockade?

Extrapyramidal side effects (motor symptoms like tremors, rigidity, dystonia).

What causes Parkinson’s disease?

Loss of dopamine neurons in the nigrostriatal pathway, leading to diminished dopamine in the striatum (~20% of normal levels).

How is Parkinson’s disease treated?

• L-dopa (dopamine precursor).

• Dopamine receptor agonists.

What is a major side effect of dopamine-based Parkinson’s treatments?

Can induce psychosis by stimulating dopamine pathways.

What are the mechanisms of anticonvulsant drugs?

• Inhibit Na+ channels → Reduce action potential firing.

• Inhibit Ca2+ channels → Limit neurotransmitter release.

• Enhance GABA activity → Increase inhibition.

• Inhibit glutamate receptors → Reduce excitatory signaling.

How do cocaine and methamphetamine affect dopamine neurotransmission?

They block the dopamine transporter, preventing dopamine reuptake and flooding the synapse with dopamine.

How does nicotine affect dopamine release?

• Normally, autoreceptors limit dopamine release.

• Nicotine blocks these autoreceptors, leading to prolonged dopamine activity in the reward pathway.

How is Alzheimer’s disease treated?

Increasing acetylcholine (ACh) availability to improve cognitive function.