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Psychopharmacological evidence for increase in receptor sensitivity following chronic morphine treatment

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Abstract

The behavioral effects of cholinergic and adrenergic agents on fixed ratio responding (FR5) were examined in control rats and in rats chronically treated with morphine (5 mg/kg/day). Tolerance to the effects of morphine on total responses was observed, but not on rate of responding. Following tolerance development, the directly acting muscarinic agonist, pilocarpine, depressed the behavior of the morphine-treated animals to a significantly greater degree than that of the controls. Similarly, drugs which directly or indirectly stimulate alpha adrenergic and central dopaminergic receptors also affected the behavior of the morphine-treated rats to a significantly greater degree. One interpretation of these findings is that muscarinic cholinergic, alpha adrenergic, and central dopaminergic receptors become supersensitive to their respective neurotransmitters during chronic treatment with morphine. Such a change in receptor sensitivity could constitute a mechanism underlying the development of tolerance to morphine.

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Authors and Affiliations

  1. Department of Psychobiology, University of California, Irvine, California, USA

    Beatriz J. Vasquez, David H. Overstreet & Roger W. Russell

  2. School of Biological Sciences, The Flinders University of South Australia, Bedford Park, South Australia, Australia

    Beatriz J. Vasquez, David H. Overstreet & Roger W. Russell

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  1. Beatriz J. Vasquez
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  2. David H. Overstreet
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  3. Roger W. Russell
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This research was supported by Grant MH18788 from the National Institute of Mental Health to Roger W. Russell.

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Vasquez, B.J., Overstreet, D.H. & Russell, R.W. Psychopharmacological evidence for increase in receptor sensitivity following chronic morphine treatment. Psychopharmacologia 38, 287–302 (1974). https://doi.org/10.1007/BF00429127

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  • DOI: https://doi.org/10.1007/BF00429127

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