Priming threshold: a novel quantitative measure of the reinstatement of cocaine self-administration

Brain Res. 1999 Jun 12;831(1-2):165-74. doi: 10.1016/s0006-8993(99)01423-7.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Benzazepines / pharmacology
  • Cocaine / pharmacology*
  • Dextroamphetamine / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Tolerance
  • Infusions, Intravenous
  • Injections, Intravenous
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Self Administration


  • Benzazepines
  • Cocaine
  • Dextroamphetamine