Physical dependence and tolerance development after chronic exposure to low levels of morphine in the rat

Kosersky, Donald S.; Kowolenko, M.D.; Howes, John F.

doi:10.1016/0091-3057(80)90199-9

Cited by 5 publications

(2 citation statements)

References 6 publications

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“…In our first study (Eikelboom & Stewart, 1979), we found that the conditioned hypothermia was stronger in animals injected daily with 200 mg/kg of morphine than in animals receiving smaller doses of morphine, suggesting that conditioned hypothermia was a function of the degree of dependence induced. It has recently been demonstrated, however, that withdrawal symptoms can be elicited without the administration of such large doses of morphine (Kosersky, Kowolenko, & Howes, 1980). As in other conditioned withdrawal studies, the conditioned temperature responses in our experiments mimicked the withdrawal hypothermia.…”

Section: Conditioned Changes In Body Temperaturesupporting

confidence: 81%

Conditioning of drug-induced physiological responses.

Eikelboom

Stewart²

1982

Psychological Review

372

200

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An analysis of the conditioning of drug effects is presented that permits the prediction of the nature and direction of conditioned responses and accounts for drug-conditioning results within stimulus-substitution theory. It is argued that the failure to define and identify correctly the unconditioned stimulus effect and the unconditioned response effect of a drug constitutes the source of the controversies about the relation of the conditioned response to the observed drug effect. A model is provided for specifying the site of action of a drug with respect to feedback systems and regulatory mechanisms, and methods for identifying the site of action are discussed. The ideas presented are relevant to studies of conditioned drive, to drug tolerance and sensitization, and to conditioning studies that do not involve drugs.Repeated administration of drugs often results in the conditioning of physiological responses. These conditioned responses can be distinguished from other direct and indirect drug effects by the fact that under appropriate circumstances, they can be elicited without administering the drug. This form of classical conditioning is important because it may occur whenever drugs are chronically administered. The drug administration ritual may act as the conditioned stimulus and come to elicit a conditioned response. These conditioned responses have been postulated to play a role in drug tolerance and sensitization (Siegel, 1975b(Siegel, , 1977b, in drug abuse (Grabowski & O'Brien, 1981;Lynch, Stein, &Fertziger, 1976;Wilder, 1948 Wilder, , 1973b,and in behavioral medicine (Woods & Kulkosky, 1976). However, the reader who sets out to find an explicit role for conditioned drug effects in specific situations is faced with a mass of contradictory findings and confusing interpretations. The most common of these

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Section: Conditioned Changes In Body Temperaturesupporting

confidence: 81%

Conditioning of drug-induced physiological responses.

Eikelboom

Stewart²

1982

Psychological Review

372

200

View full text Add to dashboard Cite

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“…The timing of the trial was based on substantial literature demonstrating that passive opioid withdrawal symptoms persist for at least a week in rats after a brief chronic treatment regimen. [45][46][47] The second experiment evaluated the ability of rapastinel to blunt relapse after a brief (5 day) conditioned place preference paradigm. Rapastinel treatment was initiated during extinction from CPP, again paralleling potential clinical practice, and its effect on relapse after a probe dose of morphine was tested.…”

Section: Introductionmentioning

confidence: 99%

Rapastinel Accelerates Loss of Withdrawal Signs after Repeated Morphine and Blunts Relapse to Conditioned Place Preference

Armstrong

Ferrante

Lamichhane

et al. 2022

Preprint

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The purpose of the present study was to evaluate the efficacy of rapastinel, an allosteric modulator of NMDA receptor function, to accelerate the loss of opioid withdrawal symptoms and blunt or prevent relapse to morphine conditioned place preference (CPP) in rats. Two studies were conducted. In study 1, adult and adolescent male and female rats were treated with increasing doses of morphine (5 mg/kg, bid to 25 mg/kg bid) for 5 days. On day 6 animals were treated with naloxone (1 mg/kg) and withdrawal was assessed. They were then treated with saline or rapastinel (5 mg/kg) on days 6 and 8, and withdrawal assessed on day 9. Rapastinel treated animals exhibited significantly lower levels of withdrawal signs on day 9. No sex or age differences were observed. In Study 2, CPP for morphine was established in adult rats (males and females) by 4 daily pairings with saline and morphine (am/pm alternation). They were tested for CPP on day 5, and then treated with rapastinel (5 mg/kg) or saline daily on days 6-10 of extinction. On day 11 they received a final dose of rapastinel or saline followed by extinction. On day 12, animals received 1 mg/kg of morphine and were tested for relapse. Rapastinel did not affect extinction of CPP, but rapastinel-treated animals spent significantly less time in the previously morphine-paired side than saline-treated animals during the relapse trial. These findings of accelerated loss of withdrawal signs and blunted relapse to CPP suggest that rapastinel could provide an adjunctive therapy for opioid dependence during initiation of pharmacotherapy for opioid dependence.

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