Facilitation of 5-HT2A/2C-mediated neurotransmission in the ventromedial hypothalamic nucleus decreases anxiety in the elevated T-maze

Previous evidence has shown that facilitation of GABA/benzodiazepine-mediated neurotransmission in the ventromedial hypothalamus (VMH) inhibits both escape and inhibitory avoidance responses generated in the elevated T-maze test of anxiety (ETM). These defensive behaviors have been associated with panic and generalized anxiety, respectively. Aside from GABA/benzodiazepine receptors, the VMH also contains a significant number of serotonin (5-HT) receptors, including 1A, 2A and 2C subtypes. The purpose of the present study was to investigate the effect of the activation of 5-HT1A and 5-HT2A/2C receptors in the VMH on defensive behavioral responses in rats submitted to the ETM. For that, male Wistar rats were treated intra-VMH with the 5-HT1A agonist 8-OH-DPAT, with the 5-HT2A/2C agonist DOI, with the 5-HT2C selective agonist MK-212, or with the 5-HT2A/2C antagonist ketanserin and 10 min after were submitted to the ETM. Results showed that both DOI and MK-212 significantly decreased avoidance measurements, an anxiolytic-like effect, without altering escape. 8-OH-DPAT and ketanserin were without effect, although the last drug attenuated the effects of DOI. None of the drugs altered locomotor activity in an open field. These results suggest that 5-HT2A/2C receptors of the VMH are involved in the regulation of inhibitory avoidance and might be of relevance to the physiopathology of generalized anxiety.

Research highlights▶ 5-TH2 receptors activation in the ventromedial hypothalamus facilitates avoidance. ▶ Escape performance is not modified. ▶ 5-HT1A receptors activation is also without effect. ▶ 5-HT2 receptors of the ventromedial hypothalamus play a selective role in anxiety.