β-adrenergic regulation of circadian locomotor activity and anesthetic emergence in mice.

Abstract

β2-adrenergic receptors (β2-ARs) are target of catecholamines such as noradrenaline and belong to the family of G protein-coupled receptors. They are distributed in many organs, including the central nervous system. Genetic and pharmacological tools targeting β2-ARs indicate that they mediate a variety of physiological responses. However, their role in the central nervous system remains elusive. Here, we employed β2-adrenergic receptor-deficient (β2-AR KO) mice to elucidate β2-AR role in regulating circadian locomotor activity as well as emergence from general anesthesia. We found that loss of β2-ARs significantly delayed emergence from anesthesia in β2-AR KO mice of both sexes, indicating involvement of β2-adrenergic signaling pathway in the transition from unconsciousness to complete wakefulness. Behaviorally, general locomotor activity in the dark phase and light-to-dark transitions was significantly lower in β2-AR KO mice than in wild type mice of both sexes, whereas dark to light transitions were decreased in β2-AR KO males only. Given that β-ARs play an important role in regulating cardiovascular function and that changes in cardiac performance may induce changes in locomotor activity, heart rate and systolic function were evaluated by echocardiography. These parameters did not differ significantly between KO and wild type mice, suggesting that altered locomotor behaviors in KO mice are not mediated by changes in cardiac performance. Together, these data reveal the functional importance of β2-adrenergic signaling for anesthetic emergence and circadian locomotor activity suggesting that these processes can be affected by drugs which cross the blood-brain barrier and bind to β2-ARs such as lipophilic, non-selective β-blockers.