Changes in behavioral sensitivity to SKF-38393 and quinpirole following withdrawal from continuous cocaine administration in rats

The effects of withdrawal from continuous administration of cocaine on spontaneous locomotor activity and behavioral sensitivity to SKF-38393 and quinpirole were examined in rats. Subdermal minipumps that delivered either saline or 20 mg/kg/day cocaine hydrochloride were implanted for 14 days. Spontaneous locomotor activity, SKF-38393-induced (10 mg/kg, SC) grooming and tongue protrusions, and quinpirole-induced locomotor activity and stereotypy (0.32 and 1.0 mg/kg, SC) were examined either 4-5 h or 7 days after removal of the minipumps. Animals withdrawn from cocalne for 4 h exhibited a decrease in spontaneous locomotor activity relative to saline-pretreated controls, whereas animals withdrawn for 7 days did not differ from controls. Animals withdrawn from cocaine for 4 h did not differ from controls in their sensitivity to SKF-38393, whereas animals withdrawn from cocaine for 7 days exhlbited an increase in SKF-38393-induced tongue protrusions relative to controls. In contrast, animals withdrawn from cocaine for 4 h exhibited a decrease in quinpirole-induced locomotion, whereas animals withdrawn for 7 days did not differ from controls. There were no differences in sensitivity to quinpirole-induced stereotypy relative to controls at either withdrawal period. These findings suggest that an increased sensitivity of D₂-like receptors emerges within 7 days during the course of withdrawal from continuous cocaine administration, whereas a change in sensitivity of D₂-like receptors may occur early during withdrawal but normalizes within 7 days.