The effects of idazoxan and other alpha 2-adrenoceptor antagonists on food and water intake in the rat.

1. Idazoxan (1, 3, 10 mg kg-1, 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 alpha 2-adrenoceptor antagonists, RX811059 (0.3, 1, 3 mg kg-1, i.p.) and RX821002 (0.3, 1, 3 mg 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 alpha 2-adrenoceptor antagonist, L-659,066 (1, 3, 10 mg kg-1, i.p.), did not affect food intake in the 4 h following injection, but the highest dose (10 mg kg-1), produced a large increase in water intake. 4. These results indicate that alpha 2-adrenoceptor antagonists may increase water intake by a peripherally mediated mechanism. 5. The lack of effect 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 alpha 2-adrenoceptor blockade but may instead reflect its affinity for a non-adrenoceptor site, a property not shared by the other alpha 2-antagonists.