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Alprazolam and oxazepam block the cue-induced reinstatement of extinguished cocaine seeking in rats

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Abstract

Rationale

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.

Materials and 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.

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Authors and Affiliations

  1. Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, P.O. Box 33932, 1501 Kings Highway, Shreveport, LA, 71130, USA

    Nicholas E. Goeders, David M. Clampitt, Courtney Keller, Mukesh Sharma & Glenn F. Guerin

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  1. Nicholas E. Goeders
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  2. David M. Clampitt
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  3. Courtney Keller
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  4. Mukesh Sharma
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  5. Glenn F. Guerin
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Corresponding author

Correspondence to Nicholas E. Goeders.

Additional information

This work was supported in part by USPHS grant DA06013 from the National Institute on Drug Abuse.

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Goeders, N.E., Clampitt, D.M., Keller, C. et al. Alprazolam and oxazepam block the cue-induced reinstatement of extinguished cocaine seeking in rats. Psychopharmacology 201, 581–588 (2009). https://doi.org/10.1007/s00213-008-1326-1

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  • DOI: https://doi.org/10.1007/s00213-008-1326-1

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