Abstract
Phencyclidine (also known as PCP or ”angel dust”) is a hallucinogen that causes not only euphoria, excitation, and disordered thinking, but also psychotic episodes and violent behavior. Phencyclidine is a noncompetitive antagonist at N-methyl-d-aspartate (NMDA) receptors, and its effects in animals have been used as a model of the psychotic aspects of schizophrenia. The forebrain serotonin system originates in the raphe nuclei in the midbrain, including the dorsal raphe nucleus (DRN) and median raphe nucleus (MRN). Neurotoxin lesions of the MRN, but not DRN, markedly enhanced the effects of phencyclidine in rats. This enhancement was also observed after serotonin depletion in the dorsal hippocampus, but not the ventral hippocampus, amygdala, or frontal cortex. Serotonergic projections arising from the MRN are suggested to exert a tonic inhibitory effect on the dorsal hippocampus, and removal of this inhibitory loop allows enhancement of phencyclidine effects. Thus, there is a direct relationship between the effects of phencyclidine and activity of the serotonin system in the hippocampus.
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