Are the analgesic effects of social defeat mediated by benzodiazepine receptors?

Rodgers, R.J.; Randall, J.I.

doi:10.1016/0031-9384(87)90364-7

Cited by 36 publications

(4 citation statements)

References 54 publications

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“…Our findings that diazepam alone had no antinociceptive activity at any dose up to 5 mg/kg is in conflict with several observations in the literature which indicate an antinociceptive effect of benzodiazepines (Sierralta and Miranda, 1992;Jimenez-Velazquez et al, 2008;Jimenez-Velazquez et al, 2010) but in agreement with others who found no antinociceptive effect of benzodiazepines (Rodgers and Randall, 1987;Rosland et al, 1987;Moreau and Pieri, 1988). In addition to the effects of benzodiazepines on antinociception alone, there are as well mixed findings on the interactions between this class of drugs and opioid actions.…”

Section: Reversal Of Morphine Analgesic Tolerance By Ethanolcontrasting

confidence: 67%

Reversal of Morphine Analgesic Tolerance by Ethanol in the Mouse

Hull

Gabra

Bailey³

et al. 2013

J Pharmacol Exp Ther

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The chronic use of opioids in humans, accompanied by the development of tolerance, is a dangerous phenomenon in its own right. However, chronic opioid use is often made more dangerous by the coconsumption of other substances. It has been observed that the blood level of opioids in postmortem analyses of addicts, who consumed ethanol along with the opioid, was much less than that observed in individuals who died from opioids alone. This relationship between ethanol and opioids led us to investigate the hypothesis that ethanol alters tolerance to opioids. In the present study, we report that ethanol significantly and dose-dependently reduced the antinociceptive tolerance produced by morphine and the cross-tolerance between [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) and morphine in the mouse tail-flick test. The reversal of morphine tolerance was partially blocked by both the gamma receptor blocker bicuculline and by the g-aminobutyric acid (GABA) B receptor blocker phaclofen and the administration of both inhibitors completely reversed the effects of ethanol on morphine tolerance. Diazepam, like ethanol, decreased morphine tolerance. However, this inhibition was reversed by the GABA A antagonist bicuculline but not by the GABA B antagonist phaclofen. These findings have important implications for individuals who abuse opioids and ethanol as well as suggest a mechanism to reduce the amount of opioid needed in chronic pain treatment.

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Section: Reversal Of Morphine Analgesic Tolerance By Ethanolcontrasting

confidence: 67%

Reversal of Morphine Analgesic Tolerance by Ethanol in the Mouse

Hull

Gabra

Bailey³

et al. 2013

J Pharmacol Exp Ther

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show abstract

“…A more ethological approach to the study ofbenzodiazepine administration and the blockage of analgesia has been reported by Rodgers and Randall (1987a, 1987b, 1988a, 1988b. These experimenters administered benzodiazepines during resident-intruder sessions and tested for analgesia both before and after such sessions.…”

Section: Methodsmentioning

confidence: 99%

“…Experimental procedures similar to those involving benzodiazepines have been used with the 5-HT lA system in analgesia (Rodgers & Randall, 1987a;Rodgers & Shepherd, 1989a, 1989b. Again, an increase in analgesia was blocked if 5-HT lA autoreceptor agonists were administered prior to resident-intruder sessions, as compared with a prestressor level of responding to pain.…”

Section: Methodsmentioning

confidence: 99%

Conditioned fear and analgesia to conspecific odors: Benzodiazepine and 5-HT1A agonists

Hotsenpiller

Williams

1996

Psychobiology

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“…In addition to the reported influence of stress on benzodiazepine binding (op cit. ), several other lines of evidence led us to propose that non-opioid intruder analgesia may be mediated by an endogenous ligand for benzodiazepine binding sites: (a) acute stress rapidly decreases GABA binding in brain, an effect mimicked by benzodiazepine receptor inverse agonists (Biggio et al 1981;Biggio 1983;Corda and Biggio 1986), and (b) benzodiazepine receptor inverse agonists exert anxiogenic effects in a variety of animal models (Pellow and File 1984c;Stephens et al 1986) and are reported to have significant analgesic efficacy (Rodgers and Randall 1987 a). In support of this tentative hypothesis, diazepam and Ro15-1788 have been found to totally block defeat analgesia in DBA/2 mice (Rodgers and Randall 1987a) and scent analgesia in deer mice (Kavaliers and Innes 1988).…”

mentioning

confidence: 99%

Blockade of non-opioid analgesia in intruder mice by selective neuronal and non-neuronal benzodiazepine recognition site ligands

Rodgers

Randall

1988

Psychopharmacology

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In male mice, the biologically significant experience of social defeat is associated with an acute non-opioid form of analgesia. Recent studies have shown that this reaction is sensitive to certain benzodiazepine receptor ligands but is unaffected by others. The present experiments were designed to assess the possibility that activity at "non-neuronal" benzodiazepine binding sites might account for this unusual pharmacological profile. Our results show that defeat analgesia was blocked by clonazepam (0.06-3 mg/kg), Ro05-4864 (2.5-20 mg/kg), Ro05-5115 (20 mg/kg), PK11195 (5-20 mg/kg) and PK14067 (10-20 mg/kg). Furthermore, when given in combination, subthreshold doses of PK11195 (2.5 mg/kg) and clonazepam (0.03 mg/kg) totally prevented defeat analgesia. All of these effects were observed in the absence of intrinsic activity on basal nociception. Together with earlier findings, current data imply that inhibition of defeat analgesia by ligands for neuronal and/or non-neuronal benzodiazepine recognition sites is most probably unrelated to their activity at these sites. Alternative explanations for the overall patterns of results are considered.

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Are the analgesic effects of social defeat mediated by benzodiazepine receptors?

Cited by 36 publications

References 54 publications

Reversal of Morphine Analgesic Tolerance by Ethanol in the Mouse

Reversal of Morphine Analgesic Tolerance by Ethanol in the Mouse

Conditioned fear and analgesia to conspecific odors: Benzodiazepine and 5-HT1A agonists

Blockade of non-opioid analgesia in intruder mice by selective neuronal and non-neuronal benzodiazepine recognition site ligands

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