Direct and indirect 5-HT receptor agonists produce gender-specific effects on locomotor and vertical activities in C57 BL/6J mice.

It is well established that the dopamine (DA) and serotonin (5-HT) systems have extensive and complex interactions. However, the effects of specific 5-HT receptor agonists on traditionally DA-related behaviors remain unclear. Our goal in these studies was to characterize the effects of 5-HT receptor agonists on measures of locomotor activity and vertical rearing. The SSRIs fluoxetine and citalopram produced significant decreases in locomotor activity and vertical rearing at the highest doses used with females significantly more sensitive to citalopram. The 5-HT(1A) agonist 8-OH-DPAT and the 5-HT(2C) agonist MK 212 significantly decreased activity in both male and female mice, with females more sensitive to 8-OH-DPAT. In contrast, the 5-HT(1B) agonist RU 24969 and the 5-HT(2A) agonist DOI both increased activity, with DOI exhibiting differential effects with regard to sex. Finally, the 5-HT(3) agonist SR 57227 produced significant locomotor increases only in female mice at the lowest dose. The results of these experiments define locomotor profiles of several 5-HT agonists in male and female C57BL/6J mice, providing a foundation for further explorations of 5-HT receptor effects on activity.