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Selective mu- and kappa-opioid receptor antagonists administered into the nucleus accumbens interfere with rapid tolerance to ethanol in rats

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Abstract

Background

Previous findings have shown that intra-accumbens injection of naltrexone, a non-selective opioid antagonist, blocks the acquisition of rapid tolerance to ethanol in rats. This study investigates the effects of intra-accumbens injection of the selective mu-, delta-, and kappa-opioid antagonists, respectively, naloxonazine, naltrindole, and nor-binaltorphimine, on rapid tolerance to ethanol.

Methods

Male Wistar rats with guide cannulae directed to the shell or the core portions of the nucleus accumbens received a microinjection of naloxonazine (2–4 μg), naltrindole (2–4 μg), nor-binaltorphimine (2.5–5 μg), or vehicle. After 5 min, each group was divided in two groups that received ethanol (2.7 g/kg i.p.) or saline. Rats were then tested for motor coordination on the tilting plane apparatus. Twenty four hours later, all rats received a challenge dose of ethanol (2.7 g/kg i.p.) and were tested on the tilt plane again.

Results

Repeated injections of ethanol caused a reduction in motor impairment suggesting the development of tolerance. However, rats injected with 4 μg naloxonazine into either core or shell portions of the nucleus accumbens did not exhibit tolerance when challenged with ethanol on day 2. Rats treated with 5 μg nor-binaltorphimine into accumbens core plus intraperitoneal saline on day 1 showed reduced motor impairment when challenged with ethanol on day 2, suggesting cross-tolerance to ethanol.

Conclusions

Taken together, our results suggests that mu-opioid receptors in both shell and core portions of the nucleus accumbens, and possibly kappa-opioid in the core, participate in the modulation of rapid tolerance to ethanol.

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Abbreviations

NLZ:

Naloxonazine

NTD:

Naltrindole

BNI:

Nor-binaltorphimine

VEH:

Vehicle

E:

Ethanol

S:

Saline

NMDA:

N-methyl-d-aspartic acid

GABA:

γ-Aminobutyric acid

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Acknowledgments

This study was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; Grant 472829/2003-3). We thank Dr. R.N. Takahashi, Dr. G.A. Rae, and Dr. D.D. Savage for their helpful comments. We also thank Drs. J. Marino-Neto and Z.L. Bouzon for their technical assistance in the histological analyses. R.K. Varaschin received a Studentship from CNPq and G.S. Morato is a Research Fellow of CNPq—Brazil (501007-2003-2). All procedures were carried out in accordance with the Brazilian Society of Neurosciences and Behavior, Animal Care Guidelines and approved by our institutional ethics committee (259/CEUA/UFSC).

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  1. Departamento de Farmacologia, Centro de Ciências Biológicas, CCB, Universidade Federal de Santa Catarina, Campus Universitário Trindade, 88049-900, Florianópolis, Santa Catarina, Brazil

    Rafael Koerich Varaschin & Gina Struffaldi Morato

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Correspondence to Rafael Koerich Varaschin.

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Varaschin, R.K., Morato, G.S. Selective mu- and kappa-opioid receptor antagonists administered into the nucleus accumbens interfere with rapid tolerance to ethanol in rats. Psychopharmacology 206, 85–96 (2009). https://doi.org/10.1007/s00213-009-1582-8

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