Alprazolam and oxazepam block the cue-induced reinstatement of extinguished cocaine seeking in rats.
BACKGROUND
We have previously reported that pretreatment with benzodiazepines reduces intravenous cocaine self-administration in rats.


OBJECTIVE
This experiment was designed to investigate whether or not benzodiazepines would also inhibit the reinstatement of cocaine seeking induced by the presentation of a conditioned reinforcer.


METHODS
Adult male rats were implanted with jugular catheters and trained to self-administer cocaine (0.25 mg/kg/infusion) during daily 2-h sessions. During training, cocaine delivery was paired with the presentation of a tone and the illumination of a houselight. Once a stable baseline of cocaine self-administration was observed, lever pressing was extinguished to less than 20% of baseline rates. During reinstatement testing, responding resulted in the presentation of the conditioned reinforcer (i.e., the houselight and tone previously paired with self-administered cocaine).


RESULTS
The response-contingent presentation of the conditioned reinforcer reliably reinstated cocaine seeking. Pretreatment with alprazolam (2 or 4 mg/kg, ip) or oxazepam (20 or 40 mg/kg, ip) reversed the conditioned reinforcer-induced reinstatement of extinguished cocaine-seeking behavior at doses that did not reliably affect the conditioned reinforcer-induced reinstatement of extinguished food seeking, suggesting that benzodiazepines may not have reduced reinstatement responding due to non-specific reductions in behavior.


CONCLUSIONS
These data suggest that benzodiazepines may be useful in blocking the ability of environmental cues to stimulate cocaine seeking.
Goeders
Nicholas E
NE
Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, P.O. Box 33932, 1501 Kings Highway, Shreveport, LA 71130, USA. ngoede@lsuhsc.edu
Clampitt
David M
DM
Keller
Courtney
C
Sharma
Mukesh
M
Guerin
Glenn F
GF
D000525:Alprazolam / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016739:Behavior, Addictive; D001522:Behavior, Animal; D003042:Cocaine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological; D008297:Male; D010076:Oxazepam / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D012646:Self Administration
D014151:Anti-Anxiety Agents; D010076:Oxazepam; D003042:Cocaine; D000525:Alprazolam
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