Abstract

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.