Blockade of dopamine receptors reverses the behavioral effects of endogenous enkephalins in the Nucleus caudatus but not in the Nucleus accumbens: differential involvement of delta and mu opioid receptors.
We have previously (Daugé et al. 1988) demonstrated that injection of the mu agonist [D-Ala2, MePhe4, Gly-ol5]-enkephalin (DAGO) or the delta agonist [D-Thr2, Leu5]-enkephalyl-Thr6 (DTLET) into the rat Nucleus accumbens (N.Acc.), or Nucleus caudatus (N.Caud.) induced a hypoactivity followed by hyperactivity 150 min later in the case of the mu agonist and a hyperactivity in the case of the delta agonist. Moreover, naloxone reversible delta-type responses were obtained by local infusion of kelatorphan, ([(R)-3(N-hydroxylcarboxamido-2-benzylpropanoyl)-L-alanine]), a complete inhibitor of enkephalin catabolism, suggesting a tonic control of the behavioral activity of rat by the endogenous opioid peptides. In this work, the putative involvement of the dopaminergic system in these behavioral responses was investigated by using the DA antagonist thioproperazine. In the N.Acc., the behavioral effects of kelatorphan or of mu or delta agonists were not altered by thioproperazine-induced blockade of dopamine receptors. In contrast, the hyperactivity produced by DTLET or by kelatorphan in the N.Caud. was reversed by thioproperazine while the time-dependent biphasic effect resulting from DAGO injection remained unaffected by the DA antagonist. This blocking effect of thioproperazine is in agreement with the previously described delta-selective enhancement of the release of newly synthesized DA in the striatum but not in the N.Acc.
Daugé
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V
Laboratoire de Pharmacologie, UER des Sciences Pharmaceutiques et Biologiques, Paris, France.
Rossignol
P
P
Roques
B P
BP
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D002421:Caudate Nucleus / Q000187:drug effects / Q000502:physiology*; D004151:Dipeptides / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D010640:Phenothiazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000502:physiology; D011957:Receptors, Opioid / Q000502:physiology; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D012686:Septal Nuclei / Q000502:physiology*
D004151:Dipeptides; D004745:Enkephalins; D009842:Oligopeptides; D010640:Phenothiazines; D011954:Receptors, Dopamine; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C042591:kelatorphan; C037653:deltakephalin; D001058:Apomorphine