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Comparison of the behavioural effects induced by administration in rat nucleus accumbens or nucleus caudatus of selective μ and δ opioid peptides or kelatorphan an inhibitor of enkephalin-degrading-enzymes



213 96 96 3 3 Valérie Dauge Paul Rossignol Bernard P. Roques Laboratoire de Pharmacologie UER des Sciences Pharmaceutiques et Biologiques 4 avenue de l'Observatoire F-75006 Paris France Département de Chimie Organique U 266 INSERM, UA 498 CNRS, UER des Sciences Pharmaceutiques et Biologiques 4 avenue de l'Observatoire F-75006 Paris France Abstract The effects of selective agonists for δ opioid receptors: (D-Thr 2 , Leu 5 )-enkephalyl-Thr 6 (DTLET) and μ receptors: (D-Ala 2 , MePhe 4 , Gly-ol 5 )-enkephalin (DAGO) and of (R)-3-(N-hydroxyl-carboxamido-2-benzylpropanoyl)-L-alanine (kelatorphan), a complete inhibitor of enkephalin degrading enzymes, on the motor activity of rats was examined after their local administration into the nucleus accumbens (NA) or nucleus caudatus (NC). In both structures DTLET dose dependently enhanced locomotor activity as measured in the open-field test. This strong effect was reversed by the selective δ antagonist: ICI 174,864. Contrastingly, DAGO induced hypoactivity followed by hyperactivity 150 min later. This biphasic effect was blocked by systemic injection of naloxone, but not by ICI 174,864. The physiological relevance of these effects was ascertained by the naloxone-reversible stimulatory responses induced by kelatorphan, supporting a role for endogenous enkephalins in the control of behavior through δ receptor stimulation.



PsychopharmacologySpringer Journals

Published: Nov 1, 1988

DOI: 10.1007/BF00216060

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