Activation of the brain 5-HT2C 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 3mg/kg) and the preferential 5-HT(2C) receptor agonist MK212 (0.7 and 1mg/kg) induced hypolocomotion during novelty exposure. The selective 5-HT(2C) receptor antagonist SB242084 (0.3mg/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 (30microg) 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 (3mg/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.
Stiedl
Oliver
O
Center for Neurogenomics and Cognitive Research (CNCR) and Institute of Neurosciences (INW), Vrije Universiteit Amsterdam, The Netherlands. oliver@cncr.vu.nl
Misane
Ilga
I
Koch
Melanie
M
Pattij
Tommy
T
Meyer
Michael
M
Ogren
Sven Ove
SO
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002319:Cardiovascular System / Q000187:drug effects; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004338:Drug Combinations; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D004338:Drug Combinations; D044405:Receptor, Serotonin, 5-HT2C; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists