Effects of dopamine supersensitivity on lateral hypothalamic self-stimulation in rats

Dopamine (DA) receptor supersensitivity was demonstrated by potentiated d-amphetamine stereotype after a three-day treatment regimen in which the DA receptor blocker pimozide (4.0 mg/kg) was administered twice daily. Similarly-induced DA supersensitivity produced a significant increase in the rate of lever-pressing for lateral hypothalamic (LH) intracranial self-stimulation (ICSS) and a significant decrease in ICSS thresholds. No change from pretreatment baselines was observed in vehicle-treated control animals. Following three-day treatment with the noradrenaline--(NA) and DA-receptor blocker, haloperidol (4.0 mg/kg twice daily), a single injection of the alpha-adrenergic agonist clonidine (0.15 mg/kg) caused increased running behavior. In contrast clonidine decreased running in rats pretreated with chronic pimozide or vehicle. These results indicate an increase in the sensitivity of central NA receptors following chronic haloperidol but not chronic pimozide. Taken together, these findings were interpreted as a potentiation in the reinforcing properties of LH-ICSS after chronic pimozide treatments due to increases in the sensitivity of DA and not NA receptors.