Activation of the brain 5-HT_2C receptors causes hypolocomotion without anxiogenic-like cardiovascular adjustments in mice

The present study evaluated whether hypolocomotion elicited by subcutaneous administration of the non-specific 5-HT/preferential 5-HT_2C receptor agonist mCPP during novelty exposure was due to an enhanced anxiety-like state. The effects of mCPP on exploratory behavior during exposure to a new environment (novelty) were studied in male C57BL/6N mice. Subcutaneous injection of mCPP (1 and 3 mg/kg) and the preferential 5-HT_2C receptor agonist MK212 (0.7 and 1 mg/kg) induced hypolocomotion during novelty exposure. The selective 5-HT_2C receptor antagonist SB242084 (0.3 mg/kg) reversed the mCPP-induced hypolocomotion into hyperlocomotion. In contrast, MK212 induced hypolocomotion that was blocked by SB242084, indicating a specific 5-HT_2C receptor involvement. When injected intracerebroventricularly, mCPP (30 μg) elicited hypolocomotion, whereas the same dose mildly increased locomotion when injected into the dorsal hippocampus. Since anxiety affects autonomic functions, effects of mCPP on cardiovascular function were studied by radio-telemetry in the home cage of unrestrained mice. Subcutaneous injection of mCPP (3 mg/kg) had no significant effect on heart rate and mean arterial blood pressure. In summary, in view of lack of autonomic effects, and the lack of hypoactivity upon forebrain stimulation, the hypolocomotion induced by systemic mCPP cannot be explained by an enhanced anxiety-like state.