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Morphine training dose: A determinant of stimulus generalization to narcotic antagonists in the rat

Abstract

Rats were trained to discriminate between saline and either 1.75 or 5.6 mg/kg of morphine in a two-choice discrete-trial avoidance paradigm. Both groups of rats generalized completely to higher doses of morphine as well as to profadol and pentazocine, analgesics with narcotic antagonist properties. The dose of each test drug required to elicit drug-appropriate responding was about one-half log-unit higher in the rats trained with 5.6 mg/kg of morphine than in the rats trained with 1.75 mg/kg. Rats trained with the lower dose of morphine also generalized completely to the narcotic antagonist nalbuphine and to the non-opioid drug d-amphetamine, and generalized partially to the narcotic antagonist cyclazocine. In contrast, rats trained with the higher dose of morphine showed only partial generalization to nalbuphine and virtually none to cyclazocine and d-amphetamine. The degree of stimulus generalization to the narcotic antagonists and to d-amphetamine in the two groups of rats corresponds well with the known similarities and differences between the syndromes of subjective effects engendered by these drugs and morphine in man. These results indicate that systematic variation of the morphine training dose can facilitate characterization of the discriminative stimulus properties of narcotic antagonist analgesics and enhance the value of drug discrimination procedures as a model for predicting the subjective effects of these drugs.

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Correspondence to Stephen G. Holtzman.

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Shannon, H.E., Holtzman, S.G. Morphine training dose: A determinant of stimulus generalization to narcotic antagonists in the rat. Psychopharmacology 61, 239–244 (1979). https://doi.org/10.1007/BF00432265

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Key words

  • Drug discrimination
  • Morphine
  • Naloxone
  • Narcotic antagonists
  • Amphetamine