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.
Highlights
Anxiety and depression are the common types of psychiatric disorders, with high incidence and life-long prevalence (Kessler et al, 2005; Mufaddel et al, 2013)
Two-way repeated measures (RM) ANOVA revealed a significant genotype by session interaction (Figure 5B, Fgenotype × session(2,43) = 3.827, p = 0.03), and Bonferroni’s post hoc revealed a significant higher preference for the cocaine-paired side developed in β2-AR KO and HET mice compared with WT mice, indicating β2-AR KO increased rewarding properties of cocaine
Β2-AR deletion did not change basal locomotor activity, but significantly increased locomotor activity induced by acute cocaine administration and greatly enhanced preference for cocaine, which was significantly attenuated by betaxolol, the selective β1-AR antagonist
Summary
Anxiety and depression are the common types of psychiatric disorders, with high incidence and life-long prevalence (Kessler et al, 2005; Mufaddel et al, 2013). We showed that β2-AR knock-out (KO) resulted in increased anxiety in the light-dark box and elevated plus maze tasks, decreased depression-like behavior in tail-suspension test (TST), and elevated cocaineinduced rewarding effects in locomotion and conditioned placed preference tasks. The behavioral tests were performed in the following orders: open field (OF), light/dark box and elevated plus maze tasks were carried out with the first cohort of mice (WT: n = 26–27, HET: n = 17, KO: n = 27). The tasks were taped by a digital video camera and the time mice spent in each compartment was analyzed with Clever System software (CleverSys). In the test for locomotor activity induced by acute cocaine administration, mice were placed in the OF chamber for 30 min followed by another 60 min after an injection of cocaine (20 mg/kg i.p.). The WB results were analyzed with two-tailed Student’s t-test
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