Which statement about the neurotransmitter hypothesis and antipsychotic pharmacotherapy is most accurate?

• A. Serotonin hyperactivity in the mesolimbic pathway; typical antipsychotics primarily block 5-HT receptors.
• B. Glutamate hypoactivity in the prefrontal cortex; typical antipsychotics enhance NMDA receptor signaling.
• C. Dopamine hyperactivity in the mesolimbic pathway is linked to positive symptoms; typical antipsychotics primarily block D2 receptors to reduce these symptoms.
• D. Acetylcholine excess in the basal ganglia; typical antipsychotics primarily block nicotinic receptors.

Answer: (C)

Positive symptoms in schizophrenia are best explained by excessive dopamine activity in the mesolimbic pathway. Typical antipsychotics work mainly by blocking D2 receptors in that circuit, which reduces dopaminergic transmission and helps diminish delusions and hallucinations. This directly ties the neurochemical imbalance to the drug's therapeutic effect. Other theories exist, such as glutamatergic NMDA receptor dysfunction or serotonin involvement, but typical antipsychotics do not primarily act by enhancing NMDA signaling or by targeting serotonin receptors to treat positive symptoms. In short, blocking D2 receptors in the mesolimbic pathway best accounts for both the symptoms and the medication’s mechanism.