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Reinstatement of ethanol-seeking behavior by drug cues following single versus multiple ethanol intoxication in the rat: effects of naltrexone

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Abstract

Rationale

A positive relationship exists between chronic ethanol intoxication experiences and the severity of neural hyperactivity and withdrawal seizures. An important possibility is that withdrawal reactions also influence the motivation to obtain and consume ethanol.

Objectives

To test this hypothesis, the effects of ethanol-cues on the recovery of extinguished ethanol-seeking and the reversal of this effect by naltrexone, were determined in non-dependent rats and in rats subjected to single versus repeated ethanol intoxications.

Methods

Rats were trained to self-administer and discriminate between 10% ethanol and water. Instrumental responding then was extinguished and the effects of exposure to ethanol and water cues were determined. Subsequently, rats were divided into three groups and exposed to control vapor (CTRL), to 12-day ethanol vapor prior to withdrawal (SW), or to three cycles of 3-day intoxication experiences (MW), respectively. Following intoxication, reacquisition and breaking point for ethanol self-administration and cues-induced reinstatement of drug-seeking were investigated.

Results

Ethanol cues significantly reinstated responding in the pre- and post-dependence test, but no significant differences between groups was observed. However, the ability of naltrexone to attenuate the response-reinstatement was significantly reduced in MW rats. Moreover, in the progressive ratio schedule, the breaking points for ethanol were significantly increased in the MW animals.

Conclusions

The results suggest that repeated intoxication did not enhance cue-induced reinstatement of ethanol-seeking. However, naltrexone effects on cues-induced "relapse" appear to be attenuated in MW rats.

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Acknowledgements

This is publication number 15010-NP from The Scripps Research Institute. This work was supported by NIH/NIAAA grant AA10531 (F.W.). The authors would like to thank Mike Arends for his assistance with manuscript preparation.

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Author notes

  1. Daniel Lin

    Present address: Arena Pharmaceuticals Inc., San Diego, Calif., USA

Authors and Affiliations

  1. Department of Neuropharmacology, The Scripps Research Institute, La Jolla, Calif., USA

    Roberto Ciccocioppo, Daniel Lin, Rémi Martin-Fardon & Friedbert Weiss

  2. Department of Pharmacological Science and Experimental Medicine, University of Camerino, Via Scalzino 3, 62032 , Camerino, Italy

    Roberto Ciccocioppo

Authors
  1. Roberto Ciccocioppo
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  2. Daniel Lin
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  3. Rémi Martin-Fardon
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  4. Friedbert Weiss
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Correspondence to Roberto Ciccocioppo.

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Ciccocioppo, R., Lin, D., Martin-Fardon, R. et al. Reinstatement of ethanol-seeking behavior by drug cues following single versus multiple ethanol intoxication in the rat: effects of naltrexone. Psychopharmacology 168, 208–215 (2003). https://doi.org/10.1007/s00213-002-1380-z

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  • DOI: https://doi.org/10.1007/s00213-002-1380-z

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