A quantitative rotational model for studying serotonergic function in the rat.

Unilateral injection of 5,7-dihydroxytryptamine (4 mug/4 mul) into the medial forebrain bundle of rats produced serotonin depletions of 65% and 70% in the ipsilateral corpus striatum and ipsilateral forebrain, respectively. These animals showed a dose-dependent increase in contralateral turning (rotational behavior) when pretreated with a peripheral decarboxylase inhibitor and then injected with L-5-hydroxytryptophan in doses ranging from 5 to 100 mg/kg i.p. Injections of p-chloroamphetamine, which releases endogenous stores of serotonin, produced ipsilateral turning which could be blocked by prior serotonin depletion. Systemic administration of the catecholamine drugs L-DOPA, apomorphine and D-amphetamine never elicited consistent turning in either direction in these animals. These data indicate that the turning response of rats with unilateral destruction of brain serotonin nerve terminals provides a sensitive tool for quantifiably studying changes in serotonergic function.