Role of 5-HT1A receptors in the antinociceptive action of 8-hydroxy-2-(di-n-propylamino) tetralin in the rat

The role of 5-HT_1A receptors in the antinociceptive action of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was investigated by using the shock titration test in rats. A subcutaneous injection of 300 μg/kg 8-OH-DPAT significantly raised the threshold for flinching, jumping and vocalization whereas 100 μg/kg only inhibited the flinch response. l-Propranolol and (+)-[N-tert-butyl-3-4-(2-methoxyphenyl)piperazin-1-yl-2-phenyl propanamide dihydrochloride], (+)-WAY100135, two antagonists at 5-HT_1A receptors at 10 mg/kg s.c. antagonized the effect of 300 μg/kg 8-OH-DPAT on all measures. The effect of 300 μg/kg 8-OH-DPAT on the three measures was unmodified in rats which had received 150 μg 5,7-dihydroxytryptamine intracerebroventricularly 10 days before testing. The results suggest that 8-OH-DPAT inhibits nociceptive responses by stimulating postsynaptic 5-HT_1A receptors.