5-HT1 receptor agonists attenuate the naloxone-induced jumping behaviour in morphine-dependent mice.
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.
Berthold
H
H
Preclinical Research, Sandoz Ltd., Basle, Switzerland.
Fozard
J R
JR
Engel
G
G
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002065:Buspirone / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D005260:Female; D010134:Fenclonine / Q000494:pharmacology; D019329:Idazoxan; D007211:Indoles / Q000494:pharmacology; D051379:Mice; D009021:Morphine Dependence / Q000523:psychology*; D009270:Naloxone / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D007211:Indoles; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D009270:Naloxone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010134:Fenclonine; D002065:Buspirone; D011224:Prazosin; D019329:Idazoxan