Lobeline attenuates progressive ratio breakpoint scores for intracranial self-stimulation in rats

The alkaloid lobeline inhibits the function of vesicular monoamine and dopamine transporters and diminishes the behavioral and neurochemical effects of nicotine and amphetamines. In the present study, we examined the interaction of systemic administration of lobeline on breakpoint scores on a progressive ratio (PR) schedule of intracranial self-stimulation (ICSS) of the medial forebrain bundle (MFB). Rats were run in two 30 min sessions, separated by a 10 min timeout period. At the end of the first session, each rat was injected with either 0, 0.5, 1.0 or 2.0 mg/kg (i.p.) lobeline. Positive controls known to suppress and to augment ICSS responding included the adrenergic antagonist prazosin (0, 0.5 and 2.0 mg/kg, i.p.) and the psychostimulant cocaine (0, 1.25, and 5.0 mg/kg, i.p.). Analyses of changes in average PR breakpoint scores between the 2 sessions revealed that lobeline significantly suppressed PR scores at doses of 0.5, 1.0 and 2.0 mg/kg, as did 0.5 mg/kg and 2.0 mg/kg prazosin. These changes are unlikely to reflect motoric effects of these drugs inasmuch as neither lobeline nor prazosin alter locomotion at these doses. In contrast, PR breakpoint scores were significantly increased at 5.0 mg/kg cocaine, a dose that is sufficient to elevate locomotion in the rat. These results are consistent with the view that lobeline modulates brain reinforcement processes.