5-HT1 receptor agonists attenuate the naloxone-induced jumping behaviour in morphine-dependent mice

Eur J Pharmacol. 1989 Mar 14;162(1):19-27. doi: 10.1016/0014-2999(89)90599-2.


8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and RU 24969 have been used to investigate whether 5-HT1A and 5-HT1B receptors are involved in the naloxone-induced jumping behaviour of the chronically morphine-dependent mouse. To control for possible interactions with catecholaminergic systems, the effects of alpha 1- and alpha 2-adrenoceptor antagonists were investigated. 8-OH-DPAT and RU 24969, as well as buspirone, ipsapirone and flesinoxan, were found to suppress jumping. The effects were mimicked by the alpha-adrenoceptor antagonists, idazoxan, WY 26392, yohimbine and rauwolscine. Inhibition of 5-HT synthesis with para-chlorophenylalanine (pCPA) had only minimal effects on withdrawal jumping per se; the attenuating effects of 8-OH-DPAT and RU 24969 were not altered in pCPA-pretreated animals. The effects of RU 24969 were blocked by (-)-pindolol and, stereoselectively, by (-)-SDZ 21-009. (-)-Pindolol neither influenced the action of 8-OH-DPAT nor showed any effect per se. The actions of 8-OH-DPAT and buspirone, but not of RU 24969 and idazoxan, were blocked by the 5-HT1A receptor antagonist, spiroperidol. Similarly, both haloperidol and prazosin prevented the attenuating action of 8-OH-DPAT but did not interfere with the action of RU 24969. We conclude that the actions of 8-OH-DPAT and RU 24969 are mediated by postsynaptic receptors. The 5-HT1B receptor appears to mediate the attenuating action of RU 24969; the exact mechanism of action of 8-OH-DPAT remains open but activation of an alpha 1-adrenoceptor is implicated.

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Behavior, Animal / drug effects*
  • Buspirone / pharmacology
  • Dioxanes / pharmacology
  • Female
  • Fenclonine / pharmacology
  • Idazoxan
  • Indoles / pharmacology
  • Mice
  • Morphine Dependence / psychology*
  • Naloxone / pharmacology*
  • Prazosin / pharmacology
  • Receptors, Serotonin / drug effects*
  • Tetrahydronaphthalenes / pharmacology


  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Dioxanes
  • Indoles
  • Receptors, Serotonin
  • Tetrahydronaphthalenes
  • 5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole
  • Naloxone
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Fenclonine
  • Buspirone
  • Prazosin
  • Idazoxan