Evidence that serotonin mediates some behavioral effects of amphetamine

RS Sloviter, EG Drust and JD Connor

In the rat, d-amphetamine sulfate (15--80 mg/kg) causes numerous behavioral effects including simultaneous side-to-side head weaving or head tremor, forepaw padding and splayed hindlimbs. These signs are strikingly similar to a behavioral syndrome caused by intense serotonin (5-HT) receptor activation. Experiments were designed to determine whether some of the numerous effects of amphetamine on behavior can be ascribed to actions of the drug on 5-HT mechanisms. Catecholamine depletion with alpha-methyl-p-tyrosine did not prevent the amphetamine syndrome. However, 5-HT depletion with 5,7-dihydroxytryptamine or with p-chlorophenylalanine did prevent the syndrome. The degree of syndrome inhibition by p-chlorophenylalanine was correlated with the extent of 5- HT depletion. Normal responsiveness to amphetamine in p- chlorophenylalanine-treated rats was restored by 5-hydroxytryptophan, the precursor of 5-HT. Furthermore, methysergide, a 5-HT receptor blocker, prevented the amphetamine syndrome, whereas catecholamine blockers, phenoxybenzamine and pimozide, were ineffective. The results suggest that when amphetamine causes the signs of the syndrome it does so by activating 5-HT receptors in the brain, probably by displacement of endogenous 5-HT.

Volume 206, Issue 2, pp. 348-352, 08/01/1978
Copyright © 1978 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				M. Trulson and B. Jacobs Long-term amphetamine treatment decreases brain serotonin metabolism: implications for theories of schizophrenia Science, September 21, 1979; 205(4412): 1295 - 1297. [Abstract] [PDF]