MK212, a 5-hydroxytryptamine 2C receptor agonist, reverses prepulse inhibition deficits in the medial prefrontal cortex and ventral hippocampus

Abstract

Prepulse inhibition (PPI) is disrupted in many neuropsychiatric diseases. Molecules such as 5-HT2C receptor agonists alleviate PPI deficits in rodents; however, the precise mechanisms and critical regions of the brain responsible for the reversal effect of these agonists remain inconclusive. The present study aimed to investigate the areas of the brain critical for the reversal effect of 5-HT2C receptor agonists on PPI deficits in mice. The results showed that systemic administration of the 5-HT2C receptor agonist MK212 did not affect normal PPI behavior, but reversed the PPI deficits induced by the N-methyl d-aspartate receptor antagonist MK801 in mice. In addition, the 5-HT2C receptor antagonist SB242084 had no effect on PPI behavior despite MK801 treatment. Moreover, local infusion of MK212 into the medial prefrontal cortex and ventral hippocampus, excluding the nucleus accumbens or ventral tegmental area, rescued the PPI deficits induced by MK801. These data suggest that the medial prefrontal cortex and ventral hippocampus are critical brain areas responsible for the reversal of 5-HT2C agonists on PPI deficits. The results will contribute to our current knowledge on the molecular and neural mechanisms underlying the antipsychotic effects of 5-HT2C receptor agonists, especially the neural circuits modulated by 5-HT2C receptor activity.