Effects of the serotonin 5-HT receptor agonist CP 94253 on the locomotor activity and body temperature of preweanling and adult male and female rats.

Serotonin 5-HT receptor agonists increase locomotor activity of both preweanling and adult rodents. The part played by the 5-HT receptor in locomotion is less certain, with preliminary evidence suggesting that the actions of 5-HT receptor agonists are not uniform across ontogeny. To more fully examine the role of 5-HT receptors, locomotor activity and axillary temperatures of preweanling and adult male and female rats was assessed. In the first experiment, adult (PD 70) and preweanling (PD 10 and PD 15) male and female rats were injected with the 5-HT agonist CP 94253 (2.5-10 mg/kg) immediately before locomotor activity testing and 60 min before axillary temperatures were recorded. In the second experiment, specificity of drug action was determined in PD 10 rats by administering saline, WAY 100635 (a 5-HT antagonist), or GR 127935 (a 5-HT antagonist) 30 min before CP 94253 (10 mg/kg) treatment. CP 94253 significantly increased the locomotor activity of preweanling rats on PD 10, an effect that was fully attenuated by GR 127935. Conversely, CP 94253 significantly decreased the locomotor activity of male and female adult rats, while CP 94253 did not affect the locomotor activity of PD 15 rats. Regardless of age, CP 94253 (2.5-10 mg/kg) significantly reduced the axillary temperatures of preweanling and adult rats. When considered together, these results show that 5-HT receptor stimulation activates motor circuits in PD 10 rats; whereas, 5-HT receptor agonism reduces the overall locomotor activity of adult rats, perhaps by blunting exploratory tendencies.