Relative potency of amphetamine isomers in causing the serotonin behavioral syndrome in rats.

High doses of amphetamine evoke a behavioral syndrome in man which is similar to paranoid schizophrenia. The similarities between the behavioral effects of amphetamine and the symptoms of an endogenous behavior disorder suggest a mechanistic relationship between the two states. This study deals with a specific set of behavioral signs in the rat which are caused by relatively high doses of amphetamine and are mediated by serotonin receptor activation. Experiments on the mechanism by which amphetamine evokes this behavioral syndrome reveal that the l-isomer, like the d-isomer, acts indirectly, i.e., by release of endogenous serotonin. Furthermore, when d- and l-isomers are compared on the basis of potency in causing the serotonin behavioral syndrome, the d form is between two and three times more potent than the l-isomer. This result is consistent with the greater potency of the d-isomer (approx 2 to 1) in exacerbating symptoms of paranoid psychosis in humans. The data indicate that the serotonin behavioral syndrome in rats caused by relatively high doses of amphetamine may be the experimental counterpart of the paranoid psychosis induced in man by high doses of amphetamine.