The present study was undertaken to examine whether the mechanism of action of typical and atypical antipsychotics is related in their ability to regulate key phosphorylating enzyme of adenylyl cyclase-cAMP pathway, i.e., protein kinase A (PKA). For this purpose, regulatory (R) and catalytic (Cat) activities of PKA and expression of various isoforms of regulatory and catalytic subunits were exa...

Almost 50 years ago Dahlström and Fuxe discovered serotonergic neurons in the brainstem. Much remains to learn, however, about how serotonin (5hydroxytryptamine or 5HT) modulates circuit activity. Serotonergic neurons release 5HT throughout the CNS. Accordingly, these cells influence breathing rhythms, body temperature, heart rate, pain, eating, sleep, arousal, emotion, and cognition to list a ...

The modified dopamine (DA) hypothesis of schizophrenia suggests a hyperdopaminergic state in subcortical brain regions, which is believed to cause positive symptoms, while cortical regions may show a hypodopaminergic state which is believed to generate negative and cognitive symptoms. Positive symptoms are improved by typical antipsychotic drug (APD) treatment. However, negative and cognitive s...

Serotonergic (5-HT) neurons of the dorsal raphe nucleus (DRN) and cholinergic neurons in the adjacent laterodorsal (LDT) and pedunculopontine tegmental nuclei (PPT) have together been implicated in the regulation and production of REM sleep (reviewed in McCarley et al., 1995; Jones, 1993). Several lines of evidence indicate that the activity of cholinergic neurons in the PPT is involved in the ...

s | 33 receptor antagonist DU-125530 for antidepressant treatment. Br J Pharmacol 2012; 167:1021–1034 Hughes ZA, Starr KR, Langmead CJ, Hill M, Bartoszyk GD, Hagan JJ, Middlemiss DN, Dawson LA. Neurochemical evaluation ofhe novel 5HT1A receptor partial agonist/serotonin reuptakeinhibitor, vilazodone. Eur J harmacol. 2005;510:49–57. Sanchez C, Asin KE, Artigas F. Vortioxetine, a novel antidepres...

s | 33 receptor antagonist DU-125530 for antidepressant treatment. Br J Pharmacol 2012; 167:1021–1034 Hughes ZA, Starr KR, Langmead CJ, Hill M, Bartoszyk GD, Hagan JJ, Middlemiss DN, Dawson LA. Neurochemical evaluation ofhe novel 5HT1A receptor partial agonist/serotonin reuptakeinhibitor, vilazodone. Eur J harmacol. 2005;510:49–57. Sanchez C, Asin KE, Artigas F. Vortioxetine, a novel antidepres...

Over the past several years, much research has centered on the development of small molecules that, through multivalent binding interactions, enhance the regulation of fundamental biological functions. The design of a wide range of potential therapeutics focuses on mimicking natural systems that control the biological effect of protein-ligand interactions through multivalency. In this review, t...

See related article, pages 2228–2233. In 1994 I hypothesized that “deficient central nervous system serotonergic function” is a neurobiological substrate that could account for the clustering of psychosocial, biological and behavioral characteristics that increase risk of developing cardiovascular disease.1 It is gratifying, therefore, to see in this issue of Stroke the report by Muldoon et al2...

The type 1 sodium-proton exchanger (NHE-1) is expressed ubiquitously and regulates key cellular functions, including mitogenesis, cell volume, and intracellular pH. Despite its importance, the signaling pathways that regulate NHE-1 remain incompletely defined. In this work, we present evidence that stimulation of the 5-hydroxytryptamine1A (5-HT1A) receptor results in the formation of a signalin...

One of the fundamental insights emerging from contemporary neuroscience is that mental illnesses are brain disorders. In contrast to classic neurological illnesses that involve discrete brain lesions, mental disorders need to be addressed as disorders of distributed brain systems with symptoms forged by developmental and social experiences. While genomics will be important for revealing risk, a...