Priming threshold: a novel quantitative measure of the reinstatement of cocaine self-administration.
The intravenous injection of cocaine has been reported to reliably reinstate (prime) the self-administration of cocaine in animals. We report herein that there is a cocaine priming threshold in rats trained to self-administer cocaine. The cocaine priming threshold is defined as the minimum level of cocaine in the body that will reinstate maintained cocaine self-administration. The mean cocaine priming threshold in rats was calculated to be approximately 186 to 212 microg kg(-1). Therefore, any injection, series of injections or continuous infusion that result in a level of cocaine equivalent to that produced by a single intravenous injection of this range of doses, will reinstate cocaine self-administration. The priming threshold was significantly increased by the D(1) dopamine receptor antagonist SCH23390 (10 microg kg(-1), i.v.), indicating a role for dopaminergic neurotransmission. The priming threshold, but not the inter-injection interval of maintained self-administration, was increased following withdrawal from a 7-day infusion of D-amphetamine. In addition, there was no correlation between the cocaine priming threshold and the inter-injection intervals of maintained cocaine self-administration. Therefore, the mechanisms underlying the reinstatement of cocaine self-administration are distinct from the mechanisms underlying the maintenance of cocaine self-administration and they are differentially regulated. It is possible that the priming threshold may represent a distinct target for medications development.
Norman
A B
AB
Division of Neuroscience, Department of Psychiatry, College of Medicine, University of Cincinnati, Cincinnati, OH 45267-0559, USA.
Norman
M K
MK
Hall
J F
JF
Tsibulsky
V L
VL
D000704:Analysis of Variance; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration
D001552:Benzazepines; D003042:Cocaine; D003913:Dextroamphetamine