Study of the mechanisms involved in behavioral changes induced by flunitrazepam in morphine withdrawal

Study of the mechanisms involved in behavioral changes induced by flunitrazepam in morphine... 1. 1. The attenuation of morphine withdrawal syndrome by acute benzodiazepine administration has been well documented. However, the pharmacological mechanisms implicated in this effect remain unclear. 2. 2. In this study, the possible participation of noradrenergic, serotonergic and benzodiazepine receptors on flunitrazepam-modified morphine withdrawal syndrome was investigated in mice. Flunitrazepam was associated to the noradrenergic antagonists prazosin (1 mg/kg) and propranolol (0.5 mg/kg), the serotonergic agents ritanserine (1 mg/kg) and p-chloro phenylalanine (600 mg/kg), the benzodiazepine antagonist flumazenil (10 mg/kg), and the benzodiazepine partial inverse agonist Ro 15-4513 (5 mg/kg). 3. 3. The decrease in jumping behavior-induced by flunitrazepam was potentiated by prazosin, while ritanserine, flumazenil and Ro 15-4513 blocked this effect. 4. 4. Flunitrazepam-induced increase on wet dog shake frequency was partially reduced by flumazenil, and strongly antagonized by ritanserine and Ro 15-4513. 5. 5. Noradrenergic and serotonergic systems seem to be primarily implicated in the changes induced on jumping and wet dog shakes respectively. These modifications are induced through the activation of the benzodiazepine receptors. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Progress in Neuro-Psychopharmacology & Biological Psychiatry Elsevier

Study of the mechanisms involved in behavioral changes induced by flunitrazepam in morphine withdrawal

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Publisher
Elsevier
Copyright
Copyright © 1995 Elsevier Ltd
ISSN
0278-5846
eISSN
1878-4216
DOI
10.1016/0278-5846(95)00125-F
Publisher site
See Article on Publisher Site

Abstract

1. 1. The attenuation of morphine withdrawal syndrome by acute benzodiazepine administration has been well documented. However, the pharmacological mechanisms implicated in this effect remain unclear. 2. 2. In this study, the possible participation of noradrenergic, serotonergic and benzodiazepine receptors on flunitrazepam-modified morphine withdrawal syndrome was investigated in mice. Flunitrazepam was associated to the noradrenergic antagonists prazosin (1 mg/kg) and propranolol (0.5 mg/kg), the serotonergic agents ritanserine (1 mg/kg) and p-chloro phenylalanine (600 mg/kg), the benzodiazepine antagonist flumazenil (10 mg/kg), and the benzodiazepine partial inverse agonist Ro 15-4513 (5 mg/kg). 3. 3. The decrease in jumping behavior-induced by flunitrazepam was potentiated by prazosin, while ritanserine, flumazenil and Ro 15-4513 blocked this effect. 4. 4. Flunitrazepam-induced increase on wet dog shake frequency was partially reduced by flumazenil, and strongly antagonized by ritanserine and Ro 15-4513. 5. 5. Noradrenergic and serotonergic systems seem to be primarily implicated in the changes induced on jumping and wet dog shakes respectively. These modifications are induced through the activation of the benzodiazepine receptors.

Journal

Progress in Neuro-Psychopharmacology & Biological PsychiatryElsevier

Published: Sep 1, 1995

References

  • Development of physical dependence on morphine in respect to time and dosage and quantification of the precipitated withdrawal syndrome in rats
    Blasig, J.; Herz, K.; Reinhold, K.; Zieglgansberger, S.
  • Benzodiazepine antagonist Ro 15-1788: neurological and behavioral effects
    Bonetti, E.P.; Polc, P.; Cumin, R.; Schaeffer, R.; Pieri, L.; Gamzu, E.; Muller, R.; Haefely, W.
  • Nucleus locus ceruleus: new evidence of anatomical and physiological specificity
    Foote, S.L.; Bloom, F.E.; Aston-Jones, G.
  • Influence of different benzodiazepines on the experimental morphine abstinence syndrome
    Maldonado, R.; Mic'o, J.A.; Val Verde, O.; Saavedra, M.C.; Leonsegui, I.; Gibert-Rahola, J.
  • Photoaffinity labelling of benzodiazepine-receptors with a partial inverse agonist
    Möhler, H.; Sieghart, W.; Richards, J.; Hunkeler, W.
  • Tolerance pattern to GABAmimetic analgesic and their influence on morphine tolerance and dependence
    Srinivasan, D.; Ramaswamy, S.; Bapna, J.S.; Srinivasan, B.

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