Serotonin 5-HT 2 and 5-HT 1A receptors in the periaqueductal gray matter differentially modulate tonic immobility in guinea pig

Abstract

Tonic immobility (TI) is an inborn defensive behavior characterized by a temporary state of profound and reversible motor inhibition elicited by some forms of physical restraint. We have previously reported that cholinergic stimulation of the dorsal periaqueductal gray matter (PAG) decreases the duration of TI episodes, while stimulation of the ventrolateral region increases it. The ventrolateral PAG modulates this behavior via a similar neural circuit proposed to be involved in the antinociceptive system. Some studies have indicated that alterations in the levels of cerebral 5-hydroxytryptamine (5-HT) mediate or modulate the analgesic effect of PAG stimulation. Thus, in this study we investigated the possibility that the serotoninergic system is involved in the modulation of TI by this neural substrate. Our results showed that the effect of serotonin into the ventrolateral and dorsal PAG seems to be biphasic and dose dependent. The microinjection of low doses (0.1 μg) of 5-HT into the PAG increased the duration of TI, while high doses (1, 3 and 6 μg) decreased this behavior. Our results also showed that microinjection of a 5-HT 1A agonist (0.003, 0.01 and 0.1 μg of 8-hydroxy-dipropylaminotretalin (8-OH-DPAT)) into the PAG increased the duration of TI episodes. However, the microinjection of 5-HT 2 agonist (0.01 and 0.1 μg of α-methyl-5-HT) into the PAG decreased the duration of TI and this effect could be reversed by pretreatment with an ineffective dose (0.01 μg) of ketanserin. In contrast, ketanserin (0.03 and 0.16 μg) increased this behavior in a dose-dependent manner. These results suggest that the PAG 5-HT 1A and 5-HT 2 receptors have different roles in the modulation of TI in guinea pigs, since the 5-HT 1A and 5-HT 2 agonists, respectively, increased and decreased the duration of TI.