A COMPARISON OF PSYCHOTOMIMETIC DRUG EFFECTS ON RAT BRAIN NOREPINEPHRINE METABOLISM

¹ Department of Psychiatry, Stanford Medical Center, Stanford, California and University of Chicago School of Medicine, Chicago, Illinois

The effects of LSD, psilocybin, mescaline, amphetamine and cold water swimming stress on the metabolism of ³H-norepinephrine in rat brain were determined. Graded doses (130-1300 µg/kg) of LSD showed no specific effects on brain catecholamine metabolism, suggesting that this drug had little direct activity on brain noradrenergic neurons. Psilocybin (25 mg/kg) had effects similar to those obtained with amphetamine (2 mg/ kg), as evidenced by a prominent and sustained elevation in ³H-normetanephrine content. These findings are consistent with an increased release of norepinephrine from central nerve endings. Cold water swim stress, on the other hand, resulted in a profound increase in ³H-deaminated catechol metabolites, suggesting that the intracellular catabolism of norepinephrine was affected specifically. Mescaline (25 mg/kg) had a biphasic effect on brain ³H-norepinephrine metabolism. Shortly after injection, mescaline-treated rats imad a metabolite pattern similar to animals subjected to cold water swimming; from 90 minutes to 4 hours after mescaline, however, ³H-normetanephrine levels were elevated markedly. Based on these data, mescaline appears to cause an initial increase in intracellular ³H-norepinephrine metabolism, followed by a period of enhanced release similar to the effects of amphetamine and psilocybin. These data indicate that the psychotomimetic drugs tested share no single common effect on brain norepinephrine metabolism.