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 ([symbol: see text] = 166 mm, 16 rpm; approximately 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-HT1A receptor antagonist WAY-100,635 produced an impaired performance at a low dose (12.5 micrograms kg-1 s.c.), with a recovery of performance at higher doses (50-200 micrograms 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-HT1A 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.).