Abstract

A single dose of p-chloroamphetamine, 10 mg per kilogram, produced postural abnormalities, tremor, myoclonus, and autonomic signs in rats 5 minutes after intraperitoneal injection. This syndrome lasted 60 to 90 minutes, and its intensity was directly proportional to the amount of p-chloroamphetamine given over a 2 to 10 mg per kilogram range. Whole-brain levels of serotonin and 5-hydroxyindoleacetic acid were not altered during this interval, although both were reduced significantly 1 day later. Pretreatment with drugs that interfere with the uptake of p-chloroamphetamine into terminals of serotonergic neurons (fluoxetine), depress brain serotonin levels (p-chlorophenylalanine), or block serotonin receptors (methiothepin or methergoline) suppressed this syndrome, whereas drugs that antagonize the effects of dopamine, norepinephrine, and acetylcholine did not. These observations implicate serotonergic mechanisms and provide behavioral evidence of p-chloroamphetamine's immediate actions on serotonergic neurons in the central nervous system.

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