The role of serotonin (5-hydroxytryptamine [5-HT]) and 5-HT2A receptors in anxiety has been extensively studied, mostly without considering individual differences in trait anxiety. Our laboratory developed two lines of animals that are bred for high and low freezing responses to contextual cues that are previously associated with footshock (Carioca High-conditioned Freezing [CHF] and Carioca Low-conditioned Freezing [CLF]). The present study investigated whether ketanserin, a preferential 5-HT2A receptor blocker, exerts distinct anxiety-like profiles in these two lines of animals. In the first experiment, the animals received a systemic injection of ketanserin and were exposed to the elevated plus maze (EPM). In the second experiment, these two lines of animals received microinjections of ketanserin in the infralimbic (IL) and prelimbic (PL) cortices and were exposed to either the EPM or a contextual fear conditioning paradigm. The two rat lines exhibited bidirectional effects on anxiety-like behavior in the EPM and opposite responses to ketanserin. Both systemic and intra-IL cortex injections of ketanserin exerted anxiolytic-like effects in CHF rats but anxiogenic-like effects in CLF rats. Microinjections of ketanserin in the PL cortex also exerted anxiolytic-like effects in CHF rats but had no effect in CLF rats. These results suggest that the behavioral effects of 5-HT2A receptor antagonism might depend on genetic variability associated with baseline reactions to threatening situations and 5-HT2A receptor expression in the IL and PL cortices.Highlights CHF and CLF rats are two bidirectional lines that are based on contextual fear conditioning.CHF rats have a more “anxious” phenotype than CLF rats in the EPM.The 5-HT2A receptor antagonist ketanserin had opposite behavioral effects in CHF and CLF rats.Systemic and IL injections either decreased (CHF) or increased (CLF) anxiety-like behavior.PL injections either decreased (CHF) anxiety-like behavior or had no effect (CLF).

No abstract

Exposure to adverse childhood experiences or early life stress experiences (ELSs) increase the risk of non-adaptive behaviors and psychopathology in adulthood. Environmental enrichment (EE) has been proposed to minimize these effects. The vast number of methodological variations in animal studies underscores the lack of systematicity in the studies and the need for a detailed understanding of how enrichment interacts with other variables. Here we evaluate the effects of environmental enrichment in male and female Wistar rats exposed to adverse early life experiences (prenatal, postnatal, and combined) on emotional (elevated plus maze), social (social interaction chamber), memory (Morris water maze) and flexibility tasks. Our results—collected from PND 51 to 64—confirmed: 1) the positive effect of environmental enrichment (PND 28–49) on anxiety-like behaviors in animals submitted to ELSs. These effects depended on type of experience and type of enrichment: foraging enrichment reduced anxiety-like behaviors in animals with prenatal and postnatal stress but increased them in animals without ELSs. This effect was sex-dependent: females showed lower anxiety compared to males. Our data also indicated that females exposed to prenatal and postnatal stress had lower anxious responses than males in the same conditions; 2) no differences were found for social interactions; 3) concerning memory, there was a significant interaction between the three factors: A significant interaction for males with prenatal stress was observed for foraging enrichment, while physical enrichment was positive for males with postnatal stress; d) regarding cognitive flexibility, a positive effect of EE was found in animals exposed to adverse ELSs: animals with combined stress and exposed to physical enrichment showed a higher index of cognitive flexibility than those not exposed to enrichment. Yet, within animals with no EE, those exposed to combined stress showed lower flexibility than those exposed to both prenatal stress and no stress. On the other hand, animals with prenatal stress and exposed to foraging-type enrichment showed lower cognitive flexibility than those with no EE. The prenatal stress-inducing conditions used here 5) did not induced fetal or maternal problems and 6) did not induced changes in the volume of the dentate gyrus of the hippocampus.

No abstract

No abstract