Dopaminergic mechanisms in precipitated withdrawal in morphine-dependent rats.

Rats were made dependent on morphine by implantation of a pellet and withdrawal was precipitated by the injection of naloxone 72 hours later. Withdrawal was assessed by scoring each of the following signs individually: chewing, licking, teeth chattering, facial tremor, grooming, writhing, diarrhea, weight loss, wet dog shakes, head shakes and hypothermia. The role of dopamine in withdrawal was determined by pretreating the animals with apomorphine or pimozide. Apomorphine in the lower dose range (0.625-1.25 mg/kg) produced a significant decrease in teeth chattering, writhing, weight loss and wet dog shakes. The high dose of apomorphine (2.5 mg/kg) significantly inhibited all features of the withdrawal except writhing and weight loss. Pimozide caused a significant increase in chewing, writhing and head shakes, but only with the highest dose used (0.5 mg/kg). Pimozide (0.5 mg/kg) significantly reduced withdrawal hypothermia, but apomorphine had no effect on this sign except at the highest dose when withdrawal hypothermia was increased.