Antagonism of reserpine-induced suppression of spontaneous motor activity by stimulation of 5-HT1A receptors in rats.

The 5-HT1A and the DA D2 receptor agonists 8-OH-DPAT (0.05-3.2 mg kg-1 subcutaneously, -20 min.) and quinpirole (0.08-1.25 mg kg-1 subcutaneously, -20 min.), respectively, both partially antagonized reserpine-induced (5 mg kg-1 subcutaneously, -16 hr) suppression of spontaneous motor activity in the rat. Four different aspects of the spontaneous motor activity were recorded in a photocell-equipped open-field (8 x 8 photocells, 90 mm apart, defining two horizontal planes): locomotor activity (all photocell counts at the lower level); rearing (all photocell counts at the upper level); forward locomotion (the proportion movements across the arena); peripheral activity (the proportion locomotor activity as picked up by the photocell beam closest to the wall, i.e. 25 mm). As defined by these variables, the pattern of activity produced by 8-OH-DPAT or quinpirole were indistinguishable. The effects produced by 8-OH-DPAT were fully antagonized by the 5-HT1 antagonist (-) pindolol (4 mg kg-1 subcutaneously, -30 min.), but not by the DA D2 receptor antagonist raclopride (2 mg kg-1 subcutaneously, -30 min.) nor by the 5-HT2 receptor antagonist ritanserin (2 mg kg-1 subcutaneously, -30 min.), whereas effects produced by quinpirole were fully antagonized by raclopride (2 mg kg-1 subcutaneously, -30 min.). Effects produced by quinpirole, but not 8-OH-DPAT, were potentiated by administration of the DA D1 agonist SKF-38,393 (3 mg kg-1 subcutaneously, -20 min.). It is concluded that effects by 8-OH-DPAT on spontaneous motor activity in the reserpine treated rat primarily are due to stimulation of postsynaptic 5-HT1A receptors.