Biphasic effects of 8-OH-DPAT on endurance of treadmill performance in the male rat

Administration of the 5-HT1A receptor agonist 8-OH-DPAT produced a biphasic pattern of effects on endurance performance of rats walking on top of a treadmill drum (0 = 166 mm, 16 rpm; approximate to 8 m min(-1)), with enhanced performance at a low dose (0.1 mg kg(-1) s.c.) followed by impairment (0.2-0.8 mg kg(-1)). The partial 5-HT1A receptor agonist (-)-pindolol improved the performance in the low dose range (0.5-2.0 mg kg(-1) s.c.), whereas a higher dose (8 mg kg(-1)) was ineffective. The 5-HT,, receptor antagonist WAY-100,635 produced an impaired performance at a low dose (12.5 mu g kg(-1) s.c.), with a recovery of performance at higher doses (50-200 mu g kg(-1)). It is suggested that the inhibition of central serotonergic neurotransmission produced by stimulation or blockade of 5-HT1A auto- and post-synaptic receptors, respectively, results in an improved endurance performance on the treadmill, whereas stimulation of postsynaptic 5-HT,, receptors has the opposite action. In support of this contention, the impaired performance produced by a high dose of 8-OH-DPAT (0.8 mg kg(-1)) was antagonized by pretreatment with (-)-pindolol (2 mg kg(-1) s.c.). (C) 1997 Elsevier Science B.V.