Naloxone-precipitated abstinence in mice, rats and gerbils acutely dependent on morphine

Ramabadran, K.

doi:10.1016/0024-3205(83)90523-4

Cited by 22 publications

(11 citation statements)

References 9 publications

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“…Similarities in antagonist-precipitated changes after chronic and acute administration of morphine also have been observed for a variety of dependent measures in several animal models (Kosersky et al 1974;Eisenberg 1982;Krystal and Redmond Jr 1983;Ramabadran 1983;Schnur 1991;Easterling and Holtzman 1997). Additionally, naloxone after a single dose of morphine induces subjective symptoms that are identified as withdrawal by subjects with a history of opiate use (Bickel et al 1988;Heishman et al 1989;June et al 1995).…”

Section: Introductionmentioning

confidence: 82%

Discriminative stimulus effects of acute morphine followed by naltrexone in the squirrel monkey

White

Holtzman

2003

Psychopharmacology

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This is the first non-rodent study of the discriminative effects of MOR-->NTX. MOR-->NTX produces a unique interoceptive stimulus that is pharmacologically selective, requires occupation of opioid receptors, presumably mu, for some minimum period of time, and is reversible. This discrimination procedure might provide new insights into the early drug-receptor interactions that underlie the development of physical dependence upon morphine-like drugs.

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Section: Introductionmentioning

confidence: 82%

Discriminative stimulus effects of acute morphine followed by naltrexone in the squirrel monkey

White

Holtzman

2003

Psychopharmacology

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“…The observation of an acute dependence state as defined by antagonist-precipitation of somatic withdrawal signs following acute pretreatment with opiates has been reported in a number of other species, including monkeys (Krystal and Redmond 1983), dogs (Martin and Eades 1964;Jacob and Michaud 1974), hamsters (Schnur et al 1992), mice (Cheney and Goldstein 1971;Kosersky et al 1974;Smits 1975;Wiley and Downs 1979;Ritzmann 1981;Ramabadran 1983;Sofuoglu et al 1990), and rats and gerbils (Ramabadran 1983). Many of these studies reported naloxone-induced jumping behavior in morphine-pretreated mice, and typically high doses of morphine (50-150 mg / kg) were used (e.g.…”

Section: Introductionmentioning

confidence: 95%

Opiate withdrawal signs precipitated by naloxone following a single exposure to morphine: potentiation with a second morphine exposure

1997

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Recent studies in humans with no prior history of opiate abuse indicated that naloxone-precipitated signs of opiate withdrawal could be observed after a single exposure to morphine, and that the severity of withdrawal was enhanced following a second morphine exposure 24 h later. The current study was conducted to establish a paradigm in rodents that resembled these conditions described in humans. To that end, naloxone-precipitated (0.03-3.0 mg/kg) suppression of operant response rates and somatic signs of withdrawal following single or repeated treatments with morphine (5.0 mg/kg) were assessed in previously opiate-naive rats. In one group of rats, naloxone was administered 4 h after both the first and second morphine pretreatment, while in a separate group of rats naloxone was administered 4 h after the second morphine pretreatment only. A single morphine pretreatment significantly increased naloxone's potency to suppress operant response rates, and resulted in the precipitation by naloxone of certain somatic signs of withdrawal. The effects of naloxone on both dependent measures (operant response rates and somatic signs) were potentiated following a second morphine pretreatment, regardless of whether naloxone was administered following both morphine exposures or only following the second morphine exposure. Thus, repeated morphine administration appears to be the critical factor underlying the progressive increase in antagonist potency, whereas prior experience with naloxone is not a necessary factor. The results provide additional support for the hypothesis that the development of dependence on opiates is a progressive phenomenon that may begin with a single dosing.

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“…The assessment of acute opioid dependence in animal subjects, most frequently rodents, typically has focused on: 1) somatic indices of withdrawal (Martin and Eades 1964;Cheney and Goldstein 1971;Jacob and Michaud 1974;Jacob et al 1974;Smits 1975;Wiley and Downs 1979;Ritzmann 1981;Ramabadran 1983;Sofuoglu et al 1990;Schnur et al 1992;Schulteis et al 1997Schulteis et al , 1999, and 2) suppression of operant responding (SOR) by low doses of opiate antagonists (Meyer and Sparber 1977;Adams and Holtzman 1990;White-Gbadebo and Holtzman 1994;Schulteis et al 1997Schulteis et al , 1999. Antagonist-precipitated SOR also is well characterized as a sensitive index of withdrawal from chronic opiates (Gellert and Sparber 1977;Schulteis et al 1994).…”

Section: Introductionmentioning

confidence: 99%

“…Somatic signs of withdrawal are fairly subtle following acute morphine treatment (Schulteis et al 1997(Schulteis et al , 1999, unless very high doses of either morphine, or naloxone, or both are employed (Kosersky et al 1974;Smits 1975;Wiley and Downs 1979;Ritzmann 1981;Ramabadran 1983). In contrast, SOR has been seen following administration of low doses of opioid antagonists such as naloxone (0.1-0.3 mg/kg) in rats pretreated with a single, low dose of morphine (1-5.6 mg/kg; Meyer and Sparber 1977;Young 1986;Adams and Holtzman 1990;WhiteGbadebo and Holtzman 1994;Schulteis et al 1997Schulteis et al , 1999.…”

Section: Introductionmentioning

confidence: 99%

Conditioned place aversion is a highly sensitive index of acute opioid dependence and withdrawal

2003

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Naloxone-precipitated abstinence in mice, rats and gerbils acutely dependent on morphine

Cited by 22 publications

References 9 publications

Discriminative stimulus effects of acute morphine followed by naltrexone in the squirrel monkey

Discriminative stimulus effects of acute morphine followed by naltrexone in the squirrel monkey

Opiate withdrawal signs precipitated by naloxone following a single exposure to morphine: potentiation with a second morphine exposure

Conditioned place aversion is a highly sensitive index of acute opioid dependence and withdrawal

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