Chlordiazepoxide alters intravenous cocaine self-administration in rats.
This investigation was designed to examine the effects of benzodiazepines on intravenous cocaine self-administration in rats. Pretreatment with low doses of the benzodiazepine receptor agonist, chlordiazepoxide (0.3 to 1.0 mg/kg, IP), resulted in small but nonsignificant increases in drug intake with 0.5 mg/kg cocaine, while higher doses (10 mg/kg, IP) significantly decreased drug intake in all rats tested. The effects of chlordiazepoxide on self-administration were attenuated when the concentration of cocaine was increased to 1.0 mg/kg, suggesting that chlordiazepoxide was opposing rather than augmenting the pharmacological actions of cocaine. Pretreatment with the benzodiazepine receptor antagonist, Ro 15-1788 (1.0 to 10 mg/kg, IP), had no effect on self-administration, suggesting that the reinforcing properties of cocaine do not result from direct interactions with benzodiazepine receptors. The result of this investigation demonstrate that chlordiazepoxide alters intravenous cocaine self-administration in rats. Although additional research will be necessary to confirm these data, the results of this investigation suggest that chlordiazepoxide may decrease the reinforcing efficacy of cocaine through indirect actions on dopaminergic neuronal activity potentially mediated through GABAergic mechanisms via benzodiazepine receptor activation.
Goeders
N E
NE
Department of Pharmacology & Therapeutics, Louisiana State University Medical Center, Shreveport 71130-3932.
McNulty
M A
MA
Mirkis
S
S
McAllister
K H
KH
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002707:Chlordiazepoxide / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011963:Receptors, GABA-A / Q000502:physiology*; D012054:Reinforcement, Psychology; D012646:Self Administration
D011963:Receptors, GABA-A; D005442:Flumazenil; D002707:Chlordiazepoxide; D003042:Cocaine