Positive allosteric adenosine A2A receptor modulation suppresses insomnia associated with mania- and schizophrenia-like behaviors in mice

Background: Insomnia is associated with psychiatric illnesses such as bipolar disorder or schizophrenia. Treating insomnia improves psychotic symptoms severity, quality of life, and functional outcomes. Patients with psychiatric disorders are often dissatisfied with the available therapeutic options for their insomnia. In contrast, positive allosteric modulation of adenosine A2A receptors (A2ARs) leads to slow-wave sleep without cardiovascular side effects in contrast to A2AR agonists.Methods: We investigated the hypnotic effects of A2AR positive allosteric modulators (PAMs) in mice with mania-like behavior produced by ablating GABAergic neurons in the ventral medial midbrain/pons area and in a mouse model of schizophrenia by knocking out of microtubule-associated protein 6. We also compared the properties of sleep induced by A2AR PAMs in mice with mania-like behavior with those induced by DORA-22, a dual orexin receptor antagonist that improves sleep in pre-clinical models, and the benzodiazepine diazepam.Results: A2AR PAMs suppress insomnia associated with mania- or schizophrenia-like behaviors in mice. A2AR PAM-mediated suppression of insomnia in mice with mania-like behavior was similar to that mediated by DORA-22, and, unlike diazepam, did not result in abnormal sleep.Conclusion: A2AR allosteric modulation may represent a new therapeutic avenue for sleep disruption associated with bipolar disorder or psychosis

Anelastic properties of La0.6Sr0.4Co1−yFeyO3-δ at high temperatures

The dynamic amplitude dependence of the Young's modulus and the internal friction of La0.6Sr0.4Co0.2Fe0.8O3 −δ (LSCF6428) at high temperatures were evaluated by resonance measurements. At the temperatures from room temperature to 473 K and above 1073 K, the Young's modulus of LSCF6428 was independent of the dynamic amplitude, while it gradually decreased with increasing the dynamic amplitude in the temperature range from 573 to 973 K. The above dependence was successfully explained by considering the ferroelastic behavior of LSCF6428