Diazepam alters cocaine self-administration, but not cocaine-stimulated locomotion or nucleus accumbens dopamine

Pharmacol Biochem Behav. 2008 Nov;91(1):202-7. doi: 10.1016/j.pbb.2008.07.008. Epub 2008 Jul 20.

Abstract

Cocaine is known to enhance nucleus accumbens dopamine (NAcc DA), to serve as a positive reinforcer and to produce negative effects, such as anxiety. The influence of diazepam on cocaine intake, cocaine-stimulated behavioral activity and NAcc DA was investigated using self-administration and experimenter-administered intravenous (i.v.) cocaine. In Experiment 1, rats were pretreated with diazepam (0.25 mg/kg) or saline (0.1 ml) 30 min prior to 20 daily 1-hour cocaine (0.75 mg/kg/injection) self-administration sessions. Cocaine intake increased for all animals across sessions, but was highest in diazepam-pretreated animals. Diazepam rats also self-administered their first cocaine injection of each session faster than controls. Experiment 2 utilized in vivo microdialysis to assess NAcc DA levels before and after experimenter-administered i.v. cocaine injections (0.75 mg/kg/injection x 2; 10-min interval) in diazepam- and saline-pretreated rats. Group differences were not revealed across basal and cocaine-stimulated NAcc DA assessments, indicating that diazepam did not decrease NAcc DA during cocaine self-administration. Findings that diazepam enhances cocaine self-administration and decreases cocaine response latency support the notion that cocaine-induced anxiety limits voluntary cocaine intake. It is further suggested that individual variations in cocaine-induced aversive effects may determine whether cocaine use is avoided or repeated.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Cocaine / antagonists & inhibitors*
  • Cocaine / pharmacology*
  • Conditioning, Operant / drug effects
  • Diazepam / pharmacology*
  • Dopamine Uptake Inhibitors / antagonists & inhibitors*
  • Dopamine Uptake Inhibitors / pharmacology*
  • Food
  • Hypnotics and Sedatives / pharmacology*
  • Male
  • Microdialysis
  • Motor Activity / drug effects*
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Self Administration

Substances

  • Dopamine Uptake Inhibitors
  • Hypnotics and Sedatives
  • Cocaine
  • Diazepam