Search

It is well known that 5-HT2 mechanisms modulate the defensive behavior produced by the stimulation of the dorsal periaqueductal gray (dPAG). However, in spite of the notion that past stressful experiences play a role in certain types of anxiety, only studies with the stimulation of the dPAG of rats without previous aversive experience have been conducted so far. We investigated the mediation of 5-HT2 receptors of the dPAG in rats previously submitted to contextual fear conditioning (CFC). Defensive behaviors induced by the activation of the dPAG were assessed by measuring the lowest intensity of electric current applied to this structure (threshold) able to produce freezing and escape responses during the testing sessions of CFC in which animals were placed in a context previously paired to footshocks. The 5-HT2 function of the dPAG in this condition was evaluated by local injections of α-methyl-5-HT (20 nmol/0.2 μl) and ketanserin (5 and 10 nmol/0.2 μl), selective agonist and antagonist of 5-HT2 receptors, respectively. In accordance with previous studies, α-methyl-5-HT increased the aversive thresholds (antiaversive effects) in naive rats, and injection of ketanserin into the dPAG did not produce significant effects. On the other hand, ketanserin decreased in a dose-dependent manner the freezing threshold (proaversive effect) determined by the dPAG electrical stimulation, whereas α-methyl-5-HT continued to show antiaversive effects in animals under CFC. The present results suggest that past stressful experience can produce changes in the synaptic function of 5-HT2 receptors within the dPAG with important impact on the expression of defensive behaviors. [ABSTRACT FROM AUTHOR]

Rationale: Although 5-HT2 receptors seem to play an important role in anxiety, results from numerous studies are still highly variable. Moreover, little is known about the behavioral effects of centrally administered 5-HT2 compounds in animal models of anxiety. Objective: The current study was performed to: (1) further investigate the effects of 5-HT2 receptor activation in rats exposed to the elevated plus-maze (EPM) and the open-field arena, two widely used animal models for studying anxiety and locomotor activity; and (2) evaluate the involvement of the 5-HT2 receptors within the basolateral nucleus of the amygdala (BLA) in the modulation of such effects. Methods: In the first experiment, male Wistar rats were exposed for 5 min to the EPM 27 min following intraperitoneal (i.p.) (1.0 ml/kg) injections of the preferential 5-HT2C receptor agonist 6-chloro-2[1-piperazinyl]pyrazine (MK-212) at doses of 1.0, 2.0, or 4.0 mg/kg. Control animals were injected with saline. The percentage of open-arm entries and the percentage of time spent in these arms were employed as anxiety indexes, whereas the number of closed-arm entries was calculated as indicative of locomotor activity. In the second experiment, rats were exposed for 10 min in an open-field arena to further assess the interference of the same MK-212 doses upon locomotor activity. In Experiment 3, rats were microinjected (0.2 µl) either with the mixed 5-HT2A/2C receptor antagonist ritanserin (0.5, 1.25, 2.5, and 5.0 µg) or its vehicle into the BLA 12 min following i.p. injections of saline or the intermediate dose of MK-212 (2.0 mg/kg). Fifteen minutes later, each animal was exposed to the EPM as before. Results: Whereas the highest dose of MK-212 (4.0 mg/kg) induced motor-suppressant effects in both EPM and openfield arena, the intermediate dose of the drug (2.0 mg/kg) reduced open-arm exploration without significantly affecting the number of closed-arm entries. This behavioral profile, consistent with selective anxiogenic effect in the EPM, was dose-dependently prevented by ritanserin microinfusion into the BLA. In saline-pretreated animals, however, ritanserin (all doses) was ineffective. Conclusions: MK-212 increases anxiety and decreases locomotor activity. The anxiogenic-like profile of 5-HT2 receptor activation is prevented by the blockade of 5-HT2 receptors within the BLA, which does not have an effect by itself upon basal anxiety levels triggered by the EPM. [ABSTRACT FROM AUTHOR]