The effects of idazoxan and other α₂‐adrenoceptor antagonists on food and water intake in the rat

Abstract

1 Idazoxan (1, 3, l0mgkg-', i.p.) produced a significant increase in food and water intake in freely feeding rats during the daylight phase. 2 The more selective and specific a2-adrenoceptor antagonists, RX811059 (0.3, 1, 3 mgkg 1, i.p.) and RX821002 (0.3, 1, 3mg kg 1, i.p.), did not produce hyperphagia in rats, however, the highest dose produced a significant increase in water intake. 3 The peripherally acting a2-adrenoceptor antagonist, L-659,066 (1, 3, 10mgkg-1, i.p.), did not affect food intake in the 4h following injection, but the highest dose (l0mgkg '), produced a large increase in water intake. 4 These results indicate that a2-adrenoceptor antagonists may increase water intake by a peripherally mediated mechanism. 5 The lack of effect of RX811059 and RX821002 on food intake contrasts with the large dose-related increases induced by idazoxan and suggests that the hyperphagic effects of idazoxan are not due to a2-adrenoceptor blockade but may instead reflect its affinity for a non-adrenoceptor site, a property not shared by the other a2-antagonists.

RX 821002 as a Tool for Physiological Investigation of α2‐Adrenoceptors

“…For instance, yohimbine has been shown to increase drinking behavior induced by angiotensin II (10). The enhanced water intake is a marked feature of the behavioral effects of RX 821002 when it is given alone (57,90), thereby suggesting that control of water intake is a true physiological role of central á 2 -adrenoceptors.…”

[3H]2-(2-Benzofuranyl)-2-imidazoline, a highly selective radioligand for I2-imidazoline receptor binding sites Studies in rabbit kidney membranes

“…I 2 -RBS are labelled by [ 3 H]idazoxan and other chemically related compounds (Reis et al 1992) and have been suggested to activate glial fibrillary acidic protein (GFAP) production in cortical astrocytes (Alemany et al 1995a), produce hyperphagia in rats (Jackson et al 1991), and alter Na + uptake in isolated proximal tubule cells of rabbit kindney (Bidet et al 1990), although further confirmatory investigations of these and other putative functional effects with selective I-RBS drugs are still required.…”

The reduction in alcohol intake by the 5-HT 1A agonist 8-OH DPAT and its attenuation by the α 2 adrenergic antagonist idazoxan correlates with blood glucose levels

“…This hyperphagia appears to be related to the a¦nity of idazoxan to the imidazoline binding site, since other alpha-2 adrenoceptor antagonists without this property were not able to stimulate feeding . Furthermore, Reid et al (1994) reported that methoxyidazoxan, an alpha-2 adrenergic antagonist which is devoid of a¦nity for the imidazoline binding site and does not produce hyperphagia (Jackson et al 1991), also reduced rather than enhanced alcohol intake. These Þndings suggest a possible role for the imidazoline binding site in alcohol seeking behavior.…”