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 Animals withdrawn from cocaine for 4 h exhibited a decrease in spontaneous locomotor activity relative to saline-pretreated controls, whereas animals withdrawn for 7 days did not differ from controls. Animals withdrawn from cocaine for 4 h did not differ from controls in their sensitivity to SKF-38393, whereas animals withdrawn from cocaine for 7 days exhibited an increase in SKF-38393-induced tongue protrusions relative to controls. In contrast, animals withdrawn from cocaine for 4 h exhibited a decrease in quinpirole-induced locomotion, whereas animals withdrawn for 7 days did not differ from controls.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 D1-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.
Neisewander
J L
JL
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Lucki
I
I
McGonigle
P
P
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000009:adverse effects*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004873:Ergolines / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009294:Narcotics / Q000009:adverse effects*; D019257:Quinpirole; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists; D017448:Receptors, Dopamine D2 / Q000819:agonists; D013239:Stereotyped Behavior / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000523:psychology*
D018491:Dopamine Agonists; D004873:Ergolines; D009294:Narcotics; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D003042:Cocaine