Discriminative stimulus properties of a sigma receptor agonist in the rat: role of monoamine systems.
The role of the dopaminergic, noradrenergic and serotonergic systems in the production of the discriminative stimulus (DS) properties of the sigma receptor agonist (+)-N-allylnormetazocine [(+)-NANM/(+)-SKF 10,047] was measured in rats. The partial generalization of the noradrenergic agonist clonidine with (+)-NANM and partial antagonism of (+)-NANM by yohimbine suggest that the noradrenergic system may play a role in (+)-NANM DS. Activation of the dopaminergic system by apomorphine did not produce (+)-NANM DS however, haloperidol, which binds to the sigma receptor with high affinity, antagonized (+)-NANM DS. These data suggest that the haloperidol antagonism of (+)-NANM DS is a function of antagonism at the sigma receptor rather than antagonism at the dopamine receptor. Since yohimbine does not bind to the sigma receptor, yohimbine antagonizes (+)-NANM by a mechanism different from that of haloperidol. There was no evidence to suggest serotonergic mediation of (+)-NANM DS.
Steinfels
G F
GF
E. I. du Pont de Nemours & Co., Inc., Medical Products Department, Wilmington, DE 19898.
Tam
S W
SW
Cook
L
L
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001679:Biogenic Amines / Q000502:physiology*; D001923:Brain Chemistry / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D015016:Yohimbine / Q000494:pharmacology
D001679:Biogenic Amines; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D015016:Yohimbine; C012134:SK&F 10047; D010620:Phenazocine; D006220:Haloperidol; D001058:Apomorphine; D008784:Methysergide