Anti‐anxiety effects of β3‐adrenoceptor agonists may be due to selective enhancement of lateral paracapsular GABAergic interneurons in the basolateral amygdala

Abstract

Extensive research suggests that stress‐related stimuli increase norepinephrine (NE) levels in brain regions that regulate anxiety, like the basolateral amygdala (BLA). NE, via α and β adrenoceptor (AR) activation, is thought to increase BLA excitability, thus contributing to increased anxiety. Surprisingly, recent studies have shown that systemic β3‐AR agonist exposure decreases anxiety measures, suggesting that β3‐ARs may actually inhibit BLA excitability. Therefore, we tested the hypothesis that β3‐AR agonist‐mediated anxiolysis may be due to increased BLA GABAergic inhibition. We first examined the effects of BRL37344 (BRL, selective β3‐AR agonist) on BLA GABAergic synapses arising from local feedback and lateral paracapsular (LPCS) (feed‐forward) interneurons in rat BLA slices using whole‐cell patch methods. BRL (0.5‐10μM) selectively increased LPCS‐evoked IPSCs (eIPSCs) with no effect on local eIPSCs. BRL potentiation of LPCS eIPSCs was blocked by SR59230A (β3‐AR antagonist) or by including Rp‐CAMPS in the patch pipette solution. BRL had no effect on spontaneous IPSCs or LPCS paired‐pulse ratios. Finally, bilateral intra‐BLA injection of BRL significantly reduced anxiety‐like behaviors on the elevated plus‐maze and open‐field assay. Collectively, these data suggest that β3‐AR activation selectively enhances LPCS‐mediated BLA inhibition and that increased LPCS inhibition is sufficient to decrease anxiety‐like behaviors.Funded by NIH grants AA17039 and AA17056