Lack of β2-AR Increases Anxiety-Like Behaviors and Rewarding Properties of Cocaine

Abstract

It is well known that β-adrenoceptors (β-ARs) play a critical role in emotional arousal and stressful events, but the specific contributions of the β2-AR subtype to the psychological disorders are largely unknown. To investigate whether β2-AR are involved in anxiety-like behavior and reward to addictive drugs, we conducted a series of behavioral tests on β2-AR knock-out (KO) mice. β2-AR KO mice exhibited increased preference for the dark compartment and closed arm in tests of Light/Dark box and elevated plus maze, indicating that β2-AR deletion elevates level of anxiety or innate fear. β2-AR KO mice also showed decreased immobility in tail suspension test (TST), suggesting that β2-AR deletion inhibits depression-like behavior. Interestingly, β2-AR ablation did not change basal locomotion but significantly increased locomotor activity induced by acute cocaine administration. β2-AR KO mice showed enhanced place preference for cocaine, which could be attenuated by β1-selective AR antagonist betaxolol. Consistently, β2-AR agonist suppressed cocaine-conditioned place preference (CPP). These data indicate that β2-AR deletion enhances acute response and reward to cocaine. Our results suggest that β2-AR regulates anxiety level, depression-like behavior and hedonic properties of cocaine, implicating that β2-AR are the potential targets for the treatment of emotional disorders and cocaine addiction.

Anxiolytic Effect of Carvedilol in Chronic Unpredictable Stress Model

“…Clinical and preclinical studies have already reported the anxiolytic effect of CVD, strengthening the data presented here [63,64,66,67]. However, studies addressing neuroinflammatory mechanisms underlying the action of this drug are still scarce, mainly using stress models of anxiety.…”

“…One of the mechanisms related to this dysregulation is the activation of betaadrenergic receptors in glial cells and some brain regions. Thus, the blockade of these receptors seems to be an important anxiolytic strategy already observed in animal models and human studies [63][64][65][66][67]. Indeed, we observed that CVD was superior to DVS in regulating anxiety-like alterations induced by CUS, probably due to its nonselective blockade of adrenergic receptors.…”

Repeated vagus nerve stimulation produces anxiolytic effects via upregulation of AMPAR function in centrolateral amygdala of male rats

“…β-ARs activation enhances glutamatergic transmission in CeL, via increasing presynaptic co-release of NE and glutamate ( Silberman and Winder, 2013 ), and our results showed that rVNS increased the frequency of mEPSCs in CeL, suggesting that rVNS might elevate NE levels that led to an increased neuronal activation in CeL. Importantly, the activation of β-ARs by NE is thought to mediate memory process, defensive behavior, and anxiety-like behavior ( Liang et al, 1986 ; Watanabe et al, 2003 ; Zhu et al, 2017 ). There are several findings indicate that activation of the noradrenergic system decreases anxiety-like behavior and promotes an active coping strategy in response to stressors ( Chen et al, 2019 , Khoshbouei et al, 2002 ), which is crucial for the behavioral effects of rVNS.…”

Heart rate response to cognitive load as a marker of depression and increased anxiety

“…In addition, the results showed that, unlike other psychological characteristics, only anxiety attacks showed a better association with ECG (Section 4.2). It is possible that anxiety attacks are associated with distinct β-adrenergic dysregulation ( 73 , 74 ) and psychophysiological mechanisms, compared to those seen with trait anxiety (STAI), trait depression (BDI), and self-reported episodes of depression. This could be a relevant theme for future research.…”