Oxytocin/alpha(2)-Adrenoceptor interactions in feeding responses.
The modulation of alpha(2)-adrenoceptor-induced food intake by oxytocin has been evaluated in studies on food intake and by quantitative receptor autoradiography in the hypothalamus and the amygdala of the rat. The effects of lateral intracerebroventricular administration of clonidine and oxytocin were evaluated on food intake in satiated animals. Food consumption was measured at 30, 90, 240 min and 22 h (1,320 min) after injection. The coinjection of oxytocin and clonidine was found to counteract the increase in food intake produced by clonidine (p < 0.001) in satiated rats. Receptor autoradiographic experiments showed that oxytocin significantly increased the K(d) values of [(3)H]p-aminoclonidine alpha(2)-agonist-binding sites in the hypothalamus. Effective oxytocin concentrations ranged between 0.3 and 1 nM (p < 0.05) with a maximal action of 250% at 1 nM. The B(max) value was significantly increased (p < 0.05) for all concentrations of oxytocin. In the amygdala, oxytocin also increased both the K(d) of [(3)H]p-aminoclonidine-binding sites by about 190% at 1 nM and the B(max) values at 1 and 3 nM (p < 0.05). Oxytocin (1 nM) also significantly and substantially (p < 0.01) increased the K(d) and B(max) values of the [(3)H]UK 14.304 alpha(2)-agonist-binding sites in the hypothalamus and amygdala in agreement with the results obtained with the other agonist of the alpha(2)-adrenoceptor [(3)H]p-aminoclonidine. This effect was partially blocked by the presence of the specific oxytocin receptor antagonist, CAP. These findings suggest the existence of an antagonistic oxytocin/alpha(2)-receptor interaction in the hypothalamus and amygdala that may be of relevance for the demonstrated modulation of alpha(2)-adrenoceptor-induced feeding responses by oxytocin.
Díaz-Cabiale
Z
Z
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden. Zaida.Diaz@neuro.ki.se
Narváez
J A
JA
Petersson
M
M
Uvnäs-Moberg
K
K
Fuxe
K
K
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D000068438:Brimonidine Tartrate; D003000:Clonidine / Q000494:pharmacology; D004435:Eating / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D010121:Oxytocin / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D014018:Tissue Distribution
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D000068438:Brimonidine Tartrate; D010121:Oxytocin; D003000:Clonidine