Diazepam alters cocaine self-administration, but not cocaine-stimulated locomotion or nucleus accumbens dopamine.
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.
Maier
Esther Y
EY
College of Pharmacy, Division of Pharmacology and Toxicology, University of Texas at Austin. PHAR-Pharmacology, 1 University Station A1915, Austin, TX 78712-0125, USA.
Ledesma
Ramon T
RT
Seiwell
Andrew P
AP
Duvauchelle
Christine L
CL
D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D005502:Food; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration
D018765:Dopamine Uptake Inhibitors; D006993:Hypnotics and Sedatives; D003042:Cocaine; D003975:Diazepam