Actions and interactions of amphetamine on self-stimulation in rats

The dose-response relationship for d-amphetamine (0.125-2 mg/kg, IP) and its l-isomer (0.125-3 mg/kg, IP) was studied in self-stimulation behavior of rats each with an electrode at posterior hypothalamus (PH, mainly monoaminergic) or area ventralis tegmentum (A10, dopaminergic). The drug effects increased with the dose reaching a peak (at 0.5 mg/kg with d-amphetamine and at 1.0 mg/kg with 1-amphetamine) and then decreased. The d-isomer was approximately twice as potent as the l-isomer in enhancing intracranial self-stimulation (ICSS) rate with electrodes at either site. Azaperone (mainly an alpha-adrenergic blocker) and haloperidol (an antidopaminergic neuroleptic) used in small doses (0.05 and 0.008 mg/kg respectively) which did not affect the baseline responding, blocked amphetamine-induced enhancement of ICSS in both groups of rats. Thus, amphetamine-induced facilitation of ICSS at both PH and A10 areas and its blockade by an alpha-adrenergic blocker as well as an antidopaminergic neuroleptic show the involvement of both noradrenergic and dopaminergic mechanisms in self-stimulation behavior.