Effects of intraaccumbens administration of SCH-23390 on cocaine-induced locomotion and conditioned place preference.
The effects of systemic (0-1.0 mg/kg) or intraaccumbens (0-1.0 microg/side) administration of SCH-23390 on cocaine-induced (0 or 4.2 mg/kg, i.v.) locomotion, sniffing, and conditioned place preference (CPP) were investigated in rats. After behavioral testing was completed, animals were injected with their respective dose of SCH-23390 into the nucleus accumbens (NAc), followed by a systemic injection of the irreversible antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). Receptors occupied by intraaccumbens SCH-23390, and therefore protected from EEDQ-induced inactivation, were then quantified from autoradiograms of sections labeled with 3H-SCH-23390. Systemic administration of 0.5 and 1.0 mg/kg SCH-23390 reversed cocaine-induced locomotion, sniffing, and CPP, suggesting that stimulation of D1-like receptors is necessary for these behavioral changes. Intraaccumbens administration of 1.0 microg/side SCH-23390 reversed cocaine-CPP, and this dose occupied D1-like receptors primarily in the rostral pole of the NAc. Intraaccumbens administration of 0.5 microg/side SCH-23390 reversed cocaine-induced locomotion. However, this dose occupied a similar number of D1-like receptors in the NAc as a lower and behaviorally ineffective dose of 0.1 microg/side, but occupied more receptors in the caudate-putamen relative to both the 0.1 and 1.0 microg/side doses. These findings suggest that stimulation of D1-like receptors in the NAc is necessary for cocaine-CPP, but not for cocaine-induced locomotion.
Department of Psychology, Arizona State University, Tempe 85287-1104, USA.
D A
DA
Baker
R A
RA
Fuchs
S E
SE
Specio
T V
TV
Khroyan
J L
JL
Neisewander
D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D007267:Injections; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000502:physiology*; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects
D001552:Benzazepines; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D011804:Quinolines; D011954:Receptors, Dopamine; C000470:EEDQ; D003042:Cocaine