Adenosine is a homeostatic bioenergetic network modulator that is able to affect complex networks

synergistically at different levels (receptor-dependent pathways, biochemistry, bioenergetics, and epigenetics). By affecting brain dopamine and glutamate activities, it represents a promising candidate for reversing the functional imbalance in these neurotransmitter systems believed to underlie the genesis of schizophrenia symptoms, as well as restoring homeostasis of bioenergetics. Suggestion of an adenosine hypothesis of schizophrenia further posits that adenosinergic dysfunction might contribute to the emergence of multiple neurotransmitter dysfunctions characteristic of schizophrenia via diverse mechanisms. Given the importance of adenosine in early brain development and regulation of brain immune response, it also bears direct relevance to the aetiology GSK461364 concentration of schizophrenia. Here, we provide an overview of the rationale and evidence in support of the therapeutic potential

of multiple adenosinergic targets, including the high-affinity adenosine receptors (A(1)R PLX-4720 and A(2A)R), and the regulatory enzyme adenosine kinase (ADK). Key preliminary clinical data and preclinical findings are reviewed.

This article is part of a Special Issue entitled ‘Schizophrenia’. (C) 2011 Elsevier Ltd. All rights reserved.”
“The effects of the IWR-1 purchase selective 5-HT3 receptor agonist and antagonist m-chlorophenylbiguanide (m-CPBG)

and ondansetron, respectively, were studied in adult male Wistar rats implanted for chronic sleep recordings. Microinjection of m-CPBG (2.0 and 4.0 mM) into the dorsal raphe nucleus (DRN) decreased rapid-eye-movement sleep (REMS) and the number of REM periods during the first, second, and third 2-h recording period. On the other hand, direct infusion of ondansetron (0.5-1.0 mM) into the DRN induced no significant changes in sleep variables over the 6 h of recording. Pretreatment with ondansetron (0.5 mM) antagonized the m-CPBG (2.0 mM)-induced reduction of REMS and of the number of REM periods. The data are consistent with the hypothesis that the 5-HT3 receptor is involved in the effect of DRN serotonergic neurons on brainstem structures that act to promote and induce REMS.

It is suggested that the suppression of REMS after the microinjection of m-CPBG into the DRN is related, at least in part, to the stimulation of glutamatergic interneurons that express 5-HT3 receptors. Activation of these receptors facilitates the release of glutamate, which, in turn, acts on postsynaptic N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors expressed by serotonergic neurons of the DRN and increases the release of 5-HT at postsynaptic sites. (C) 2008 Elsevier Inc. All rights reserved.