Sensitization to daily morphine injections in rats with unilateral lesions of the substantia nigra.

Morphine indirectly enhances dopaminergic activity in the nigrostriatal system, and repeated administration of morphine progressively increases the locomotor activity of rats. We used the rotational behavior model to determine if daily morphine produces an increase in turning and produces cross-sensitization to d-amphetamine and cocaine. Rats with unilateral nigrostriatal lesions received daily injections of saline or morphine (10 mg/kg). Repeated morphine administration produced a progressive increase in turning over 13 days. Next, a morphine dose-response curve (1.0-30 mg/kg) was determined. Both the saline and morphine-treated groups showed dose-dependent increases in turning, but, the peak effect in the morphine group was higher than that 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-induced 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 progressive sensitization to turning induced by morphine in the absence of cross-sensitization to turning induced by psychomotor stimulants.