Stimulant and hallucinogenic behavioral profiles of 3,4- methylenedioxymethamphetamine and N-ethyl-3,4-methylenedioxyamphetamine in rats

LH Gold, GF Koob and MA Geyer

Division of Preclinical Neuroscience and Endocrinology, Research Institute of Scripps Clinic, La Jolla, California.

The effects of methylenedioxymethamphetamine (0.63-10.0 mg/kg) and N- ethyl-methylenedioxyamphetamine (1.0-10.0 mg/kg) on locomotor and investigatory responses of rats were measured in the Behavioral Pattern Monitor system, a system designed to measure both the quantity and quality of behavioral activity. Horizontal locomotion was increased considerably by these compounds in a dose-related manner. This hyperactivity was accompanied by an initial decrease in investigatory holepokes and rearings followed by a subsequent increase at the highest doses tested. Rats injected with these phenylethylamine derivatives also exhibited thigmotaxis and a tendency to avoid the center of the experimental chamber, a behavioral profile similar to hallucinogen-like drugs. Consequently, a disruption of the spatial patterns of locomotion was also observed. Analyses of these patterns revealed an increasing tendency toward more stereotyped, predictable locomotor paths with increasing dose. Rats circled around the perimeter of the chamber with individual animals demonstrating a predominant though not completely consistent direction of rotation. The methylenedioxymethamphetamine- induced increase in locomotion remained significantly elevated up to 4 hr after injection at a 10 mg/kg dose, whereas other aspects of motor activity returned to base-line levels more rapidly. Thus, methylenedioxymethamphetamine and N-ethyl-methylenedioxyamphetamine seem to possess both psychomotor stimulant properties and elements of a hallucinogen-like behavioral profile.

Volume 247, Issue 2, pp. 547-555, 11/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics

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