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Opioid operant self-administration, analgesia, stimulation and respiratory depression inμ-deficient mice

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Abstract

It is commonly thought thatμ-receptors play an important role in the reinforcing effects of opioids. In the present study, inbred strains widely divergent in CNS opiate receptor densities were used to investigate the influence of genetic variation in receptor concentration on opioid-reinforced behavior. In particular, the CXBK/ByJ mice were used as an investigative tool because of their significantly lower number of CNSμ opioid receptors. The behavioral pharmacology of opioids in theμ-deficient CXBK/ByJ mice was compared to other commonly used inbred mouse strains, C57BL/6J and BALB/cJ, and the opiate receptor rich CXBH/ByJ mice. Operant opioid reinforced behavior, opioid-induced locomotor stimulation, analgesia and respiratory depression were investigated in all four inbred strains. To assess the acquisition and maintenance of opioid reinforced behavior, oral self-administration of the potent benzimidazole opioid, etonitazene, was determined using an operant fixed-ratio schedule of reinforcement (FR 8). Acquisition of etonitazene-reinforced behavior was established in all four strains including theμ-deficient CXBK/ByJ mice. However, there were significant genetic differences in the amount of drug intake during the maintenance of opioid-reinforced behavior and extinction behavior following vehicle substitution. For example, drug intake was significantly greater in the BK versus BH mice during the maintenance phase and an extinction burst was seen in the BH but not the BK mice following vehicle substitution. Thus,μ-receptor density may not account for individual variability in the acquisition of opioid-reinforced behavior under these conditions. Sensitivity to etonitazene-induced respiratory depression, stimulation of locomotor activity and analgesia were unrelated to drug intake during self-administration sessions across these four inbred strains. These data indicate that inherited differences in CNSμ-opiate receptor concentrations do not affect acquisition of etonitazene-reinforced behavior.

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Authors and Affiliations

  1. Behavioral Pharmacology and Genetics Section, Preclinical Pharmacology Laboratory, National Institute on Drug Abuse, Addiction Research Center, Box 5180, 21224, Baltimore, Maryland, USA

    Gregory I. Elmer, Jeanne O. Pieper & Steven R. Goldberg

  2. Department of Psychology and Center on Alcoholism Substance Abuse Addictions (CASAA), University of New Mexico, 87131, Albuquerque, New Mexico, USA

    Frank R. George

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  1. Gregory I. Elmer
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  2. Jeanne O. Pieper
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  3. Steven R. Goldberg
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  4. Frank R. George
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Elmer, G.I., Pieper, J.O., Goldberg, S.R. et al. Opioid operant self-administration, analgesia, stimulation and respiratory depression inμ-deficient mice. Psychopharmacology 117, 23–31 (1995). https://doi.org/10.1007/BF02245094

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  • DOI: https://doi.org/10.1007/BF02245094

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