Serotonin in the dorsal periaqueductal gray modulates inhibitory avoidance and one-way escape behaviors in the elevated T-maze

Abstract

The dorsal periaqueductal gray has been implicated in the modulation of escape behavior, a defensive behavior that has been related to panic disorder. Intra-dorsal periaqueductal gray injection of serotonin or drugs that mimic its effects inhibits escape induced by electrical or chemical stimulation of this brainstem area. In this study, we investigate whether intra-dorsal periaqueductal gray injection of 5-HT receptor agonists attenuates escape generated by an ethologically based model of anxiety, the elevated T-maze. This test also allows the measurement of inhibitory avoidance, which has been related to generalized anxiety disorder. The effects of the 5-HT receptor agonists were compared in animals with or without a previous exposure to the open arms of the elevated T-maze. In these two test conditions, intra-dorsal periaqueductal gray injection of the endogenous agonist serotonin or the 5-HT2B/2C receptor agonist m-chlorophenylpiperazine (mCPP) enhanced inhibitory avoidance, suggesting an anxiogenic effect. The 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) impaired this response, suggesting an anxiolytic effect, and the preferential 5-HT2A receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) was ineffective. All these agonists inhibited escape behavior. Apart from mCPP, the effect on escape was detected only in animals pre-exposed to the open arm. None of the drugs tested affected locomotion in the open-field test. Taken altogether, our findings suggest that 5-HT1A and 5-HT2c receptors in the dorsal periaqueductal gray exert opposed control on inhibitory avoidance, implicating these receptors in anxiety conditioning. As previously observed in tests employing the aversive stimulation of the dorsal periaqueductal gray, 5-HT1A and 5-HT2A receptors in this brain area are involved in escape inhibition. Therefore, in different animal models, the activation of these two subtypes of receptors in the dorsal periaqueductal gray consistently attenuates the expression of a panic-related behavior.