Reversal of the antinociceptive effects of centrally-administered morphine by the benzodiazepine receptor antagonist Ro 15-1788 |
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| Authors: | Linda S. Brady Robert S. Mansbach David N. Skurdal Sheila M. Muldoon James E. Barrett |
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| Affiliation: | 1. Department of Psychiatry, Uniformed Services University of the Health Sciences F. Edward Hébert School of Medicine Bethesda, MD 20814-4799, USA;2. Department of Medical Psychology Uniformed Services University of the Health Sciences F. Edward Hébert School of Medicine Bethesda, MD 20814-4799, USA;3. Physiology Branch U.S. Army Medical Research Institute of Chemical Defense Aberdeen Proving Ground, MD 21010, USA;4. Department of Anesthesiology Uniformed Services University of the Health Sciences F. Edward Hébert School of Medicine Bethesda, MD 20814-4799, USA |
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| Abstract: | The effects of the benzodiazepine receptor antagonist, Ro 15-1788, were examined on analgesia induced by morphine after central (intracerebroventricular, i.c.v., or intrathecal, i.t.) and systemic administration. Analgesia was assessed in squirrel monkeys trained to respond under an electric shock tiltration procedure and in mice using the radiant heat tail-flick test. Central and systemic administration of morphine produced antinociceptive effects that were antagonized by 0.1 mg/kg of naloxone in both species. Ro 15-1788 antagonized the effects of morphine after central (i.c.v. or i.t.) administration but did not alter the effects of morphine given by the systemic route. This novel interaction suggests that Ro 15-1788 may be useful in pharmacologically separating neural substrates subserving opiate analgesia. |
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