Effects of isolation-rearing on intracranial self-stimulation reward of the lateral hypothalamus: baseline assessment and drug challenges

There is evidence that isolation rearing produces down-regulation of the dopamine D2 receptor. Therefore, isolation rearing should also modify the effects of D2 antagonists on intracranial self-stimulation (ICSS) reward. This study investigated the effect of isolation rearing on ICSS reward, and modulation of that reward by SCH23390, Raclopride and MK-801. Sprague-Dawley rats were reared alone (isolates) or in pairs from day 21 postnatal to day 75 postnatal. At this time, all rats were implanted with monopolar stimulating electrodes in the lateral hypothalamus. The ICSS rate-frequency curve-shift method was used to assess reward and operant motor function at baseline and after administration of SCH-23390 (D1 antagonist: 0.02, 0.06, 0.2 mg/kg), Raclopride (D2 antagonist: 0.01, 0.025, 0.06 mg/kg), and MK-801 (non-competitive NMDA receptor antagonist: 0.1, 0.2 mk/kg). Isolation-reared rats displayed similar measures of both basal reward and motor function when compared to socially reared controls. Isolation-reared rats were subsensitive to the reward decreasing effects of Raclopride. Socially reared rats were observed to have more variant baseline reward measures, and could be divided into distinctly different groups with different basal reward function. Isolation-rearing down-regulates D2 function but does not affect basal reward function, but some unknown factor in the social rearing environment did have a substantial effect on basal reward function.