Which historical pharmacological observation provided strong early support for the monoamine hypothesis of depression?
- A Reserpine, which depletes central stores of serotonin, noradrenaline, and dopamine, frequently induced depressive syndromes ✓
- B Amphetamine produced euphoria lasting several weeks after a single dose
- C Haloperidol caused parkinsonism in a proportion of treated patients
- D Imipramine was originally developed as a sedative for allergic disorders
Correct answer: A. Reserpine, which depletes central stores of serotonin, noradrenaline, and dopamine, frequently induced depressive syndromes
Explanation
Reserpine blocks vesicular storage of monoamines via VMAT2, depleting serotonin, noradrenaline, and dopamine, and its well-documented tendency to precipitate depressive illness supported the idea that low synaptic monoamines underlie depression. Conversely, agents increasing monoamine availability such as isoniazid elevated mood. Amphetamine euphoria relates to stimulant release mechanisms rather than depression causation, and haloperidol parkinsonism reflects dopaminergic blockade in the nigrostriatal pathway.
Reference: Stahl's Essential Psychopharmacology, 5th ed.
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