TCB-2, a 5-hydroxytryptamine 2A receptor agonist, disrupts prepulse inhibition in the ventral pallidum and nucleus accumbens

The 5-hydroxytryptamine 2A (5-HT_2A) receptor plays an important role in schizophrenia. The 5-HT_2A receptor is also involved in the regulation of prepulse inhibition (PPI) in rodents. The aim of this study was to determine whether selective 5-HT_2A receptor agonizts or antagonists may alter PPI in rats and to identify the critical brain regions in which the activity of 5-HT_2A receptors regulates PPI. The results showed that infusion of the 5-HT_2A receptor agonist TCB-2 into the lateral ventricle disrupted PPI, but the 5-HT_2A receptor antagonist M100907 had no such effect. In addition, local infusion of TCB-2 into the nucleus accumbens and ventral pallidum disrupted PPI, whereas the same manipulation in the medial prefrontal cortex, ventral hippocampus, and ventral tegmental area did not disrupt PPI. In conclusion, agonism of 5-HT_2A receptors in the ventral pallidum and nucleus accumbens can disrupt PPI. The ventral pallidum and nucleus accumbens are critical brain regions responsible for the regulation of PPI by serotonin. These findings contribute to the extensive exploration of the molecular and neural mechanisms underlying the regulatory effect of 5-HT_2A receptor activity on PPI, especially the neural circuits modulated by 5-HT_2A receptor activity.