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.

The reasons for the relationship between depression and chronic liver disease (CLD) are complex and multifactorial. Further research is needed to decipher the etiology and establish an optimal management approach for depression in patients, including the potential role of non-pharmacological treatments. monosodium glutamate (MSG)-treated rats are more likely to develop anxiogenic- and depressive-like behaviors, which could be related to the dysfunction of serotonergic system. In this study, partial hepatectomy (PH) was performed in MSG-treated rats and the histopathological changes were observed in orbitofrontal cortex (OFC) and liver. The effect of escitalopram, a widely used antidepressant, on neural and liver injury in this model was also examined. The MSG + PH-treated rats displayed decreased distances traveled in total, in center arena, and in the left side of arena in inner open field test (OFT), as compared to saline, saline + PH, and MSG-treated animals. The present study established that PH aggravated anxiety-like depressive behaviors in MSG-treated rats, concordant with damaged Nissl bodies (and neurites), decreased IBA-1 and Sox-2 expression in OFC and neurotransmitter disorder. Escitalopram treatment could alleviate these pathological changes as well as reduce hepatic steatosis and lipid metabolism.

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Objective. Depression is characterized with long disease length, whereas one major disadvantage of current mainstream treatment of depression is a high rate of relapse and recurrence. A sustained antidepressant activity is proposed to facilitate the prevention of relapse/recurrence. Here we compared the long-term antidepressant effect of Yueju, a traditional Chinese medicine formula, and a conventional antidepressant, fluoxetine, as well as revealing the underlying mechanism of long-term antidepressant effect of Yueju. Methods. Clinical long-term depression condition was modelled by using chronic learned helplessness (cLH) protocol in ICR strain mice. The short-term and long-term antidepressant effects of drugs were assessed with learned helplessness (LH), tail suspension test (TST), forced swim test (FST), and novelty-suppressed feeding (NSF) test. The expression of PKA, CaMKII signaling, and NR1, the NMDA receptor subunit, in hippocampus was determined. A CaMKII inhibitor (KN-62) was used to assess the role of CaMKII signaling in antidepressant effects of Yueju or fluoxetine. Results. In the mice exposed to chronic learned helplessness (cLH) procedure, administration of Yueju or fluoxetine for 3 weeks elicited comparable antidepressant effects, indicated by learned helplessness test, as well as TST and NSF. However, 5 days after termination of the 3-week-long drug administration, only mice previously treated with Yueju still showed the alleviation of depressive-like behaviors. At this time, the downregulation of PKA and p-CaMKII/CaMKII and upregulation of NMDA receptor subunit NR1 in the hippocampus were normalized in animals previously treated with Yueju. In contrast, none of the expressions of these proteins were changed in mice previously treated with fluoxetine. Interestingly, an administration of KN-62 blunted the antidepressant effect of Yueju. Conclusion. These findings showed the sustained antidepressant efficacy of chronic treatment with routine dose of Yueju and the CaMKII signaling activation may play a critical role in the sustained antidepressant response.

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