Role of 5-HT1A receptors in the ventral hippocampus in the regulation of anxiety- and panic-related defensive behaviors in rats.

Changes in 5-HT1A receptor (5-HT1AR)-mediated neurotransmission in the hippocampus have been associated with anxiety, depression and in the mode of action of antidepressant drugs. It has been commonly accepted that whereas the dorsal pole of the hippocampus (DH) is involved in cognitive processing, the ventral pole (VH) is associated with emotional regulation. However, to date, only a few studies have directly addressed the role played by VH 5-HT1ARs in anxiety and panic processing, and their results are conflicting. Here we report that intra-VH administration of the 5-HT1A receptor agonist 8-OH-DPAT, the endogenous agonist serotonin (5-HT), or the standard anxiolytic benzodiazepine midazolam impaired the acquisition of inhibitory avoidance in the elevated T-maze (ETM) of male Wistar rats, indicating an anxiolytic effect. Conversely, local injection of the 5-HT1AR antagonist WAY-100635 caused the opposite effect. These results were equally found in the Vogel conflict test. None of these drugs interfered with locomotor activity in the open-field test, nor did they alter the expression of the escape response in the ETM, a defensive behavior associated with panic. Pre-injection of a sub-effective dose of WAY-100635 in the VH blocked the anxiolytic effect of 5-HT or 8-OH-DPAT in the Vogel test, confirming the involvement of 5-HT1AR for this behavioral effect. The effect in this test was anxiety-selective as none of the drugs affected water consumption or nociception. In conclusion, our results suggest that 5-HT1ARs in the VH play a tonic inhibitory role in anxiety processing. These receptors, however, are not involved in the regulation of panic-related escape behavior.

Unpredictable chronic prenatal stress and manifestation of generalized anxiety and panic in rat's offspring.

Often the manifestation of anxiety cannot be explained by known environmental or hereditary factors. With this perspective, it has been reported that prenatal stress may lead to emotional disturbances in the offspring. However, studies relating prenatal stress to anxiety are controversial and generally the stressors used do not mimicks the reality experienced by mothers. Thus, this investigation evaluated the effects of an unpredictable chronic stress scheme applied in one of the three gestational weeks of rats on the manifestation of generalized anxiety and panic disorder in the progeny (males), analyzing, respectively, the avoidances and escapes in the elevated T-maze, at the 1st, 3rd or 6th month of progeny life. Control offspring showed increased generalized anxiety disorder and reduced panic at 6 months. The effects of prenatal stress depended on the gestational week where it occurred and on the progeny age: during the 1st gestational week the generalized anxiety decreased in 6 month old rats. Animals in the 3rd month, prenatally stressed during the last gestational week, showed anxiogenesis and panicogenesis, but effects reverted at the 6th month, when they presented anxiolysis and no changes related to panic. Together the results show that not only the gestational period in which the aversive experience occurred was important, but the age of the evaluated progeny, since the type and the intensity of behaviors related to anxiety may vary with the developmental stage. For the model of stress used in the present study, the effects of prenatal stress were more prominent when the exposure occurred during the 3rd gestational week in rats.

Impact of social separation during pregnancy on the manifestation of defensive behaviors related to generalized anxiety and panic throughout offspring development.

The multiple insecurities, anatomical, physiological and psychological changes arising from the gestational period can generate an overload of stress in the mother and cause disturbances in the offspring, affecting it throughout its development. The existing analysis linking prenatal stress and offspring's anxiety have divergent results, being limited as to gestational week, type of stressor and age of progeny's assessment. Social separation has been described as a stressor that causes increase in anxiety. Thus, the present study evaluated the effects of social separation applied in one of the three gestational weeks of rat dams on the manifestation of the defensive behaviors related to generalized anxiety disorder and panic in the Elevated T Maze of the male progeny in three stages of development (1, 3 or 6 months of life). It was found, in the offspring of grouped (control) dams, increased behaviors associated with generalized anxiety disorder and a reduction of panic-like behaviors throughout development. For animals whose dams were socially separated during pregnancy, the most critical period of exposure was the 2nd gestational week, which affected the acquisition of aversive memory, demonstrated by the impairment on learning of avoidances of the offspring in all ages evaluated. Stressor exposure in this week also increased the avoidances, related to generalized anxiety of progeny in the 1st month and decreased escapes, related to panic in the 3rd month of life and, at the age of 6 months old, an inverse situation, with the reduction of the defensive behaviors associated to generalized anxiety disorder. The results show that, when assessing effects of prenatal stress on the manifestation of anxiety, not only the period of exposure is important, but also the age of offspring assessed.