Activation of GABA_A receptors in the medial prefrontal cortex produces an anxiolytic-like response

Abstract

Solati J, Hajikhani R, Golub Y. Activation of GABA A receptors in the medial prefrontal cortex produces an anxiolytic-like response.Objectives: There has been increasing evidence that the g-aminobutyric acid (GABA)ergic system is involved in the neurobiology of anxiety. The present study aimed to investigate the role of GABAergic systems in the modulation of anxiety in the medial prefrontal cortex (mPFC) of rats using the elevated plus maze test. Methods: Rats were anaesthetised with a mixture of ketamine and xylazine, and then special cannulae were inserted stereotaxically into the mPFC. After 5-7 days of recovery, the effects of intra-mPFC administration of GABAergic agents were studied. Results: Bilateral injection of the GABA A receptor agonist muscimol (0.25, 0.5 and 1 mg/rat) produces an anxiolytic-like effect, shown by significant increases in the percentage of open-arm time (%OAT) and percentage of open-arm entries (%OAE). Intra-mPFC administration of the GABA A receptor antagonist bicuculline (0.25, 0.5 and 1 mg/rat) produces significant anxiogenic-like behaviour. However, intra-mPFC injection of the GABA B receptor agonist baclofen (0.05, 0.1 and 0.2 mg/rat) and the GABA B receptor antagonist CGP35348 (5, 10 and 15 mg/rat) did not alter %OAT and %OAE significantly. Conclusion:The results of the present study demonstrate that the GABAergic system of the mPFC modulates anxiety-related behaviours of rats through GABA A receptors. Significant outcomes> Anxiety behaviours of animals are controlled by the g-aminobutyric acid (GABA)ergic system of the medial prefrontal cortex (mPFC).

Oxytocin in the medial prefrontal cortex attenuates anxiety: Anatomical and receptor specificity and mechanism of action

“…First, in Experiment 3 , we show that the anxiolytic effect of OT in the PL mPFC was inhibited by concomitant treatment with the GABA A receptor antagonist BIC. Notably, higher concentrations of BIC infusions in the mPFC (> 0.25 µg) have been reported to increase anxiety (Solati et al, 2013) while the current study used a lower concentration (2.5 ng) of BIC which did not. Second, in Experiment 4, we found that the decrease in anxiety-like behavior following OT delivery to the PL mPFC was accompanied by increased activation of GAD67 neurons in this region.…”

“…Because these glutamatergic projection neurons within the PL mPFC are modulated by local GABA interneurons, which have been shown to express OTR (Marlin et al, 2015; Nakajima et al, 2014) one way OT could attenuate anxiety would be by engaging local GABAergic inhibition. This possibility is supported by evidence that OT increases GABA release in the mPFC (Qi et al, 2012) and balances cortical inhibition (Marlin et al, 2015) as well the the demonstration that activation of mPFC GABA A receptors is anxiolytic (Solati et al, 2013). Our results from Experiments 3 and 4 provide further support for an OT-GABA interaction in the PL mPFC.…”

“…Recent work has also shown that OTR are located on GABAergic interneurons (Marlin et al, 2015; Nakajima et al, 2014) in the cortex where OT has been found to increase GABA levels (Qi et al, 2012). When combined with the observation that activation of GABA A receptors in the mPFC produces an anxiolytic-like response (Mihalek et al, 1999; Solati et al, 2013), it could be postulated that OT in the PL mPFC attenuates anxiety by enhancing local GABA activity. The resulting increase in inhibition might in turn inhibit glutamatergic projections from the PL mPFC to attenuate activity of downstream limbic areas that generate anxiety-like behavior.…”

Decreasing GABA function within the medial prefrontal cortex or basolateral amygdala decreases sociability

“…Nevertheless, intra-BLA infusions of BMI, at a dose comparable to the ones used here, have previously been found to increase anxiety as measured in a conflict test [13]. Moreover, intra-PFC infusions of BMI have been found to increase anxiety as measured in the elevated plus maze; however this effect was observed following administration of BMI doses that were ten times those used in the current experiment [47]. Thus, although data from the current experiment suggests that a general increase in anxiety did not contribute to the change in social behavior, this possibility cannot currently be ruled out.…”

Timing of amphetamine exposure in relation to puberty onset determines its effects on anhedonia, exploratory behavior, and dopamine D1 receptor expression in young adulthood

“…Previous work has shown that repeated drug exposure in adult rats will also increase risk-taking behavior in other tasks (Zhou et al, 2015). Dopamine signaling in the mPFC has previously been shown to mediate decision making, including risk-based decisions (St Onge and Floresco, 2010; Simon et al, 2011), and it is noteworthy that temporary inactivation of the mPFC by local infusion of muscimol increases open arm activity (Shah et al, 2004; Solati et al, 2013). …”