Effect of the 5-HT6 serotonin antagonist MS-245 on the actions of (−)nicotine

The 5-HT6 serotonin receptor antagonist MS-245 neither substitutes for nor antagonizes the discriminative stimulus effects of (−)nicotine. However, MS-245 was shown to enhance the potency of (−)nicotine in Sprague–Dawley rats trained to discriminate 0.6 mg/kg of (−)nicotine from saline vehicle in a typical two-lever drug discrimination paradigm such that a combination of MS-245 (5.0 mg/kg) plus the ED50 dose of (−)nicotine caused the animals to respond as if they had received the training dose of (−)nicotine. MS-245 also potentiated the hypolocomotor actions, but not the antinociceptive effects, of (−)nicotine in mice. The results suggest possible involvement of serotonin-regulated signaling mechanisms in certain behavioral effects of nicotine.