EVIDENCE THAT SEROTONIN MEDIATES SOME BEHAVIORAL-EFFECTS OF AMPHETAMINE

  • 1 January 1978
    • journal article
    • research article
    • Vol. 206  (2) , 348-352
Abstract
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 were similar to a behavioral syndrome caused by intense serotonin (5-HT) receptor activation. Catecholamine depletion with .alpha.-methyl-p-tyrosine did not prevent the amphetamine syndrome. 5-HT depletion with 5,7-dihydroxytryptamine or with p-chlorophenylalanine [p-CPA] did prevent the syndrome. The degree of syndrome inhibition by p-CPA was correlated with the extent of 5-HT depletion. Normal responsiveness to amphetamine in p-CPA-treated rats was restored by 5-hydroxytryptophan, the precursor for 5-HT. Methysergide, a 5-HT receptor blocker, prevented the amphetamine syndrome. Catecholamine blockers, phenoxybenzamine and pimozide, were ineffective. Amphetamine causes the signs of the syndrome by activating 5-HT receptors in the brain, probably by displacement of endogenous 5-HT.