Effects of repeated amphetamine injections on lateral hypothalamic brain stimulation reward and subsequent locomotion.

Intracranial self-stimulation was assessed by the curve-shift method before and after D-amphetamine (1 mg/kg, i.p.) or vehicle injections given 8 times at 48-h intervals. Locomotor was assessed, in a separate test box, for the hour following the 35-min self-stimulation sessions. Amphetamine facilitated self-stimulation, shifting to the left the function relating response rate to stimulation frequency. The drug was most effective the first time it was given; the effects were weaker but unchanging across the remaining 7 days of repeated testing. When control animals that had been given vehicle for the eight initial days of testing were subsequently treated with amphetamine, it facilitated the behavior to the same extent as was seen the first time it was given in the experimental group. Amphetamine significantly increased locomotion in the period following the self-stimulation tests, and the degree of increase grew slightly but steadily with repeated testing; there was more rapid sensitization to this response in animals that were not subjected to self-stimulation testing prior to activity testing. These data do not fit well with earlier reports of sensitization to the reward-enhancing effects of amphetamine and reflect a potential dissociation between the locomotor-stimulating and reward-facilitating effects of amphetamine.