Abstract
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).
Highlights
Several studies indicate that contextual fear conditioning represents one of the simplest animal models of investigating anticipatory anxiety (Brandão et al, 2008)
The number of animals in each experimental condition in this experiment was the following: CLF animals injected with vehicle (n = 8), CLF animals injected with ketanserin (n = 10), CHF animals injected with vehicle (n = 8), and CHF animals injected with ketanserin (n = 8)
The final sample size for each group was the following: CLF animals injected with vehicle (n = 9), CLF animals injected with ketanserin (n = 11), CHF animals injected with vehicle (n = 7), and CHF animals injected with ketanserin (n = 9)
Summary
Several studies indicate that contextual fear conditioning represents one of the simplest animal models of investigating anticipatory anxiety (Brandão et al, 2008). The presence of different levels of anxiety-like behavior, that are characteristic of each line, can be assessed using several behavioral tests, including the elevated plus maze (EPM), the social interaction test and defensive responses that are induced by electrical stimulation of the dorsal periaqueductal gray (Dias et al, 2009; Galvão et al, 2010; Castro-Gomes et al, 2011, 2014; Salviano et al, 2014) These two lines represent an important tool for investigating the anxiogenic/anxiolytic pharmacological profiles of various compounds (Castro-Gomes et al, 2013). Considering the nature of anxiety as well as the presence of 5-HT2A receptors in the PL and IL cortices, the present study compared in two other experiments the effects of microinjections of the preferential 5-HT2A receptor antagonist ketanserin in the IL and PL in CHF and CLF rats in both innate (EPM) and learned (contextual fear conditioning) models of anxiety
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