RU 24969-produced adipsia and hyperlocomotion: Differential role of 5HT1A and 5HT1B receptor mechanisms

RU 24969 is a widely used, but non-selective, 5-HT1B/1A agonist that decreases fluid consumption and increases forward locomotion. The mechanism underlying these behavioural responses is not, however, well understood. Accordingly, effects of the selective 5-HT1A and 5-HT1B antagonists, WAY 100635, and GR 127935, respectively, on these two responses to RU 24969 were determined. RU 24969 (0.03-3.0 mg/kg, s.c.) dose-dependently decreased water consumption in water deprived rats. This effect was attenuated by GR 127935 (3.0 mg/kg), but not by WAY 100635 (1.0 mg/kg). RU 24969 (0.3-3.0 mg/kg) dose-dependently increased forward locomotion but a higher dose was required to produce this response than the adipsic response. The increased locomotor response was attenuated by WAY 100635 (1.0 mg/kg), but not GR 127935 (3.0 mg/kg). These results suggest that RU 24969-induced adipsia is mediated by 5-HT1B mechanisms, while RU 24969-induced hyperlocomotion is mediated by 5-HT1A mechanisms.