Blockade by naloxone of cocaine-induced hyperactivity, reverse tolerance and conditioned place preference in mice.
Cocaine-induced hyperactivity was inhibited by a single administration of naloxone (2 and 5 mg/kg, i.p.), an opioid receptor antagonist, and naloxone administered prior to and during the chronic injection of cocaine attenuated the development of both cocaine-induced reverse tolerance and conditioned place preference (CPP). Dopamine (DA) receptor supersensitivity which developed in cocaine-induced reverse tolerant or CPP mice, was also inhibited by naloxone. Furthermore, naloxone reduced an apomorphine-induced striatal dopaminergic action, climbing behavior. Therefore, the present studies suggest that cocaine-induced dopaminergic behaviors, such as hyperactivity, reverse tolerance and CPP, may be commonly produced via activation of an opioid receptor. The development of DA receptor supersensitivity may be a possible common mechanism of cocaine-induced reverse tolerance and CPP, since cocaine-induced changes in sensitivity to apomorphine, as well as apomorphine-induced climbing behavior in mice, were both inhibited by naloxone.
Kim
H S
HS
Department of Pharmacology, College of Pharmacy, Chungbuk National University, South Korea.
Park
W K
WK
Jang
C G
CG
Oh
K W
KW
Kong
J Y
JY
Oh
S
S
Rheu
H M
HM
Cho
D H
DH
Kang
S Y
SY
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004361:Drug Tolerance; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D013239:Stereotyped Behavior / Q000187:drug effects
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D003042:Cocaine; D001058:Apomorphine; D004298:Dopamine