Disulfiram facilitates the development and expression of locomotor sensitization to cocaine in rats.
BACKGROUND
Disulfiram (DS; Antabuse) inhibits dopamine-beta-hydroxylase leading to increased brain dopamine levels and shows treatment efficacy for cocaine addiction. Yet few preclinical studies have been performed. This study establishes the effects of DS on locomotor sensitization to cocaine in rats.


METHODS
Rats were administered vehicle, cocaine (10 mg/kg; intraperitoneally [IP]), or DS (50 or 100 mg/kg; IP) alone or in combination for 5 days (development phase). Locomotor activity was measured for 60-min each day. After a 10-day drug washout, rats were administered cocaine, and locomotor activity was measured (expression phase). Plasma cocaine levels were assessed in separate groups of rats administered one of two cocaine doses (0 or 10 mg/kg) and one of two DS doses (0 or 100 mg/kg) for 5 days. Ten days later, blood was collected 60-min postcocaine injection.


RESULTS
The development of cocaine locomotor sensitization was facilitated by DS even though DS alone had minimal effect on activity levels. Furthermore, expression of sensitization was greatest in rats previously administered DS, an effect that cannot be attributed to altered plasma cocaine levels.


CONCLUSIONS
Because DS shows treatment efficacy for cocaine addiction, results from this study suggest potential treatment agents should enhance, not attenuate, locomotor sensitization in rats.
Department of Neurosurgery, Thomas Jefferson Medical College, Philadelphia, Pennsylvania, USA.
Colin N
CN
Haile
Matthew J
MJ
During
Peter I
PI
Jatlow
Thomas R
TR
Kosten
Therese A
TA
Kosten
D000818:Animals; D003042:Cocaine / Q000097:blood / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000188:drug therapy*; D004221:Disulfiram / Q000494:pharmacology* / Q000627:therapeutic use; D018765:Dopamine Uptake Inhibitors / Q000097:blood / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; D003042:Cocaine; D004221:Disulfiram