Comparison of the effects of LSD and lisuride on A10 dopamine neurons in the rat

Abstract

Extracellular single-unit recording techniques were used to compare the effects of d-lysergic acid diethylamide (LSD) and its non-hallucinogenic congener lisuride hydrogen maleate (LHM) on the activity of dopamine (DA) neurons in the A10 region of the rat ventral tegmental area. Lisuride hydrogen maleate potently suppressed the firing rates of A10 DA cells (ID 50 = 0.021 mg/kg). The DA antagonist haloperidol prevented, but did not reverse, the effect of lisuride. In addition, the DA agonist apomorphine was unable to suppress further the firing rates of A10 DA cells that had been partially suppressed by small doses of lisuride. These results suggest that lisuride acted as a non-competitive or irreversible DA agonist. In contrast to lisuride, LSD exerted mixed effects on A10 DA cells, partially depressing the firing rates of 54% of the cells tested, increasing the firing rates of 23% of the cells and exerting no effect on the other 23%. The response of a particular A10 DA cell to administration of LSD was dependent upon its baseline firing rate. Haloperidol readily reversed the LSD-induced partial suppression of the firing of A10 DA cells. Also, LSD effectively reversed apomorphine-induced suppression and increased the doses of apomorphine required to suppress firing of A10 DA neurons. These results suggest that, in addition to its weak DA agonist effects, LSD also exerted partial DA antagonist effects. Pharmacological and physiological manipulations of serotonergic neuronal systems failed to implicate a role for serotonin in the effects of LSD and lisuride on A10 DA neurons. These qualitative and quantitative differences between the effects of LSD and lisuride on A10 DA neurons suggest that the potent DA agonist actions of lisuride may contribute to its lack of hallucinogenic potential.