The interplay between 5-HT_2C and 5-HT_3A receptors in the dorsal periaqueductal gray mediates anxiety-like behavior in...

The monoamine neurotransmitter serotonin (5-HT) modulates anxiety by its activity on 5-HT_2C receptors (5-HT_2CR) expressed in the dorsal periaqueductal gray (dPAG). Here, we investigated the presence of 5-HT_3A receptors (5-HT_3AR) in the dPAG, and the interplay between 5-HT_2CR and 5-HT_3AR in the dPAG in mediating anxiety-like behavior in mice. We found that 5-HT_3AR is expressed in the dPAG and the blockade of these receptors using intra-dPAG infusion of ondansetron (5-HT_3AR antagonist; 3.0 nmol) induced an anxiogenic-like effect. The activation of 5-HT_3ABR by the infusion of mCPBG [1-(m-Chlorophenyl)-biguanide; 5-HT₃R agonist] did not alter anxiety-like behaviors. In addition, blockade of 5-HT_3AR (1.0 nmol) prevented the anxiolytic-like effect induced by the infusion of the 5-HT_2CR agonist mCPP (1-(3-chlorophenyl) piperazine; 0.03 nmol). None of the treatment effects on anxiety-like behaviors altered the locomotor activity levels. The present results suggest that the anxiolytic-like effect exerted by serotonin activity on 5-HT_2CR in the dPAG is modulated by 5-HT_3AR expressed in same region.