Role of 5-HT receptor subtypes in the modulation of dorsal periaqueductal gray generated aversion

To explore the role of 5-HT receptor subtypes in controlling aversion, we measured the effect of 5-HT1A and 5-HT2A/2C receptor agonists microinjected into the dorsal periaqueductal gray (DPAG) of rats on aversive behavior induced by electrical stimulation of the same brain area. The 5-HT1A agonists 8-OH-DPAT (4-16 nmol) and BAY-R-1531 (4-16 nmol) raised the threshold of aversive electrical stimulation in a dose-dependent way. Similarly, microinjection of the 5-HT2A/2C agonist DOI (4-16 nmol) increased the aversive mCPP (16 and 32 nmol) was ineffective. Previous intra-DPAG administration of the 5-HT1A receptor blocker NAN-190 (40 nmol) antagonized the antiaversive effect of 8-OH-DPAT (8 nmol), whereas pretreatment with the 5-HT2A receptor blocker spiperone (10 nmol) antagonized the effect of DOI (16 nmol). Spiperone also counteracted the effect of 8-OH-DPAT and NAN-190 counteracted the effect of DOI. These results indicate that activation of 5-HT1A and 5-HT2A receptors inhibits aversion in the DPAG and that both receptors have to be functional for the expression of each one's activation to occur.