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Naloxone does not attenuate the locomotor effects of ethanol in FAST, SLOW, or two heterogeneous stocks of mice

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Abstract

Rationale

Previous studies suggest that some behavioral effects of ethanol and morphine are genetically correlated. For example, mice bred for sensitivity (FAST) or insensitivity (SLOW) to the locomotor stimulant effects of ethanol differ in their locomotor response to morphine.

Objective

To evaluate a possible common mechanism for these traits, we examined the effect of naloxone, an opioid receptor antagonist, on ethanol- and morphine-induced locomotion in FAST and SLOW mice, as well as on ethanol-induced locomotion in two heterogeneous stocks of mice.

Method

In experiments 1 and 2, naloxone was given to FAST and SLOW mice 30 min prior to 2 g/kg ethanol or 32 mg/kg morphine, and locomotor activity was measured for 15 min (ethanol) or 30 min (morphine). In experiments 3 and 4, naloxone was administered 30 min prior to 1.25 g/kg ethanol, and locomotor activity was assessed in FAST mice and in a heterogeneous line of mice [Withdrawal Seizure Control (WSC)]. Experiment 5 assessed the effect of naloxone on ethanol-induced stimulation in outbred National Institutes of Health (NIH) Swiss mice.

Results

There was no effect of naloxone on the locomotor response to ethanol in FAST, SLOW, WSC, or NIH Swiss mice. However, naloxone did significantly attenuate the locomotor effects of morphine in FAST and SLOW mice.

Conclusions

These results suggest that a common opioidergic mechanism is not responsible for the correlated locomotor responses to ethanol and morphine in FAST and SLOW mice, and that activation of the endogenous opioid system is not critical for the induction of ethanol-induced alterations in activity.

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Acknowledgements

This work was supported by a grant from the Department of Veterans Affairs (TJP), the Agencia Valenciana de Ciencia y Tecnología (RP), and the National Institute on Alcohol Abuse and Alcoholism, grants P50AA10760 (TJP) and T32AA07468 (SEH). The authors gratefully acknowledge the expert technical assistance provided by Sue Burkhart-Kasch, Na Li, and Christina Cotnam, as well as the helpful insight provided by Dr. Chris Cunningham. All experiments reported in this paper were performed in a manner that was consistent with the laws of the United States of America.

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Authors and Affiliations

  1. Portland Alcohol Research Center, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA

    Sarah E. Holstein, Paul J. Meyer & Tamara J. Phillips

  2. Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA

    Sarah E. Holstein, Paul J. Meyer & Tamara J. Phillips

  3. Area de Psicobiología, Universitat Jaume I, Campus de Riu Sec, 12071, Castelló, Spain

    Raúl Pastor

  4. Veterans Affairs Medical Center, R&D 32, 3710 SW US Veterans Hospital Road, Portland, OR, 97239, USA

    Tamara J. Phillips

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  1. Sarah E. Holstein
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  4. Tamara J. Phillips
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Correspondence to Tamara J. Phillips.

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Holstein, S.E., Pastor, R., Meyer, P.J. et al. Naloxone does not attenuate the locomotor effects of ethanol in FAST, SLOW, or two heterogeneous stocks of mice. Psychopharmacology 182, 277–289 (2005). https://doi.org/10.1007/s00213-005-0066-8

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  • DOI: https://doi.org/10.1007/s00213-005-0066-8

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