Sensitization to daily morphine injections in rats with unilateral lesionsof the substantia nigra

Morphine indirectly enhances dopaminergic activity in the nigrostriatal sys tem, and repeated administration of morphine progressively increases the lo comotor activity of rats. We used the rotational behavior model to determin e if daily morphine produces an increase in turning and produces cross-sens itization to d-amphetamine and cocaine. Rats with unilateral nigrostriatal lesions received daily injections of saline or morphine (10 mg/kg). Repeate d morphine administration produced a progressive increase in turning over 1 3 days. Next, a morphine dose-response curve (1.0-30 mg/kg) was determined. Both the saline and morphine-treated groups showed dose-dependent increase s in turning, but, the peak effect in the morphine group was higher than th at in the saline group, indicating sensitization to morphine. The morphine- treated group did not show cross-sensitization to either d-amphetamine (0.1 -3 mg/kg) or cocaine (1.0-30 mg/kg); in fact, it showed less cocaine-induce d turning than the saline group. Seventy-one days after saline or morphine injections began, the morphine group was still significantly more sensitive to turning induced by 10 mg/kg morphine than the saline group was (200 vs. 750). Therefore, repeated daily injections of morphine produce a progressi ve sensitization to turning induced by morphine in the absence of cross-sen sitization to turning induced by psychomotor stimulants. (C) 1999 Elsevier Science Inc.