Are 5-HT receptors or beta-adrenoceptors involved in idazoxan-induced food and water intake?
Idazoxan (10 mg/kg, i.p.) produces an unexpected increase in food intake in freely-feeding rats which has been linked to its high affinity for non-adrenoceptor idazoxan binding sites. In this study, a dose-related antagonism of idazoxan-induced food intake by the beta-adrenoceptor antagonist (-)-propranolol (5-20 mg/kg, i.p.), which also blocks 5-HT1 (5-hydroxytryptamine1) receptors has been demonstrated. (+)-Propranolol (10, 20 mg/kg, i.p.) did not attenuate idazoxan-induced feeding. (-)-Propranolol (10 mg/kg, i.p.) but not the (+)-enantiomer (10 mg/kg, i.p.) also significantly inhibited the food intake, induced by the 5-HT1A agonist 8-OH-DPAT (0.25 mg/kg, i.p.). Idazoxan-induced feeding was not altered by the selective beta-adrenoceptor antagonists betaxolol (beta 1; 5 mg/kg, i.p.) and ICI 118,551 (beta 2; 5 mg/kg, i.p.) but was potentiated by the 5-HT receptor antagonist metergoline (5 mg/kg, i.p.). The anomalous findings with metergoline may reflect its action at different sub-types of 5-HT receptor. The water intake induced by idazoxan and the peripherally-active alpha 2-adrenoceptor antagonist L-659,066 was also blocked in a stereoselective manner by propranolol (10 mg/kg) but not significantly by either metergoline (5 mg/kg, i.p.), the beta 1-adrenoceptor antagonist betaxolol (5 mg/kg, i.p.) nor by the beta 2-adrenoceptor antagonist ICI 118,551 (5 mg/kg, i.p.). These results suggest that the food intake induced by idazoxan (and perhaps mediated by non-adrenoceptor idazoxan binding sites) may involve the 5-HT system, although further studies, using antagonists acting selectively at the different sub-types of 5-HT receptor, are required to confirm this.(ABSTRACT TRUNCATED AT 250 WORDS)
Jackson
H C
HC
Reckitt and Colman Psychopharmacology Unit, Department of Pharmacology, School of Medical Sciences, University Walk, Bristol, U.K.
Nutt
D J
DJ
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D015784:Betaxolol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects*; D004435:Eating / Q000187:drug effects*; D019329:Idazoxan; D008297:Male; D008711:Metergoline / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011412:Propanolamines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011433:Propranolol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011807:Quinolizines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D013237:Stereoisomerism
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004146:Dioxanes; D011412:Propanolamines; D011807:Quinolizines; D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin; D008711:Metergoline; C055732:vatinoxan; C026777:ICI 118551; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D011433:Propranolol; D015784:Betaxolol; D019329:Idazoxan