REVERSAL OF THE RESERPINE-INDUCED SUPPRESSION OF THE CONDITIONED AVOIDANCE RESPONSE BY L-DOPA: CORRELATION OF BEHAVIORAL AND BIOCHEMICAL DIFFERENCES IN TWO STRAINS OF MICE

¹ Departments of Pharmacology and Psychiatry, The Univernity of Chicago, Chicago, Illinois

The purpose of the present experiment was to demonstrate a possible correlation between differing behavioral and biochemical responses after a single dose of 3,4-dihydroxyphenylalanine (L-dopa) in reserpine-treated mice of two different strains. Two inbred strains of mice (DBA1 and C57B1/l0) were trained to avoid shock at the sound of a buzzer, after which they were treated with reserpine (2.5 mg/kg) followed by L-dopa (400 mg/kg). The suppression of the conditioned avoidance response (CAR) after reserpine was the same for both strains. It was found, however, that the time course of CAR reversal after L-dopa was different for the two strains; the DBA mice maintained avoidance responding for a longer period than the C57 mice. To determine whether this behavioral difference could be correlated with a difference in brain catecholamine metabolism, groups of similarly treated mice of both strains were assayed at varying time intervals for dopa metabolites, dopamine and norepinephrine. The results showed 1) a reserpine-induced depletion of catecholamines to the same level in both strains and 2) after administration of L-dopa, a rise in dopamine which corresponded temporally to the period of maximal behavioral reversal of CAR suppression, i.e., 5 to 20 min postdopa injection for the C57 mice and 5 to 30 min postdopa injection for the DBA mice. Furthermore, treatment of reserpine-treated mice prior to L-dopa with Ro 4-4602/1 (400 mg/kg), an inhibitor of dopa-decarboxylase, completely blocked L-dopa reversal of CAR suppression. These results suggest that dopamine or a metabolite of dopamine is responsible for the CAR reversal after administration of L-dopa.

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