A demonstration of attentional bias, using a novel dual task paradigm, towards clinically salient material in recovering alcohol abuse patients?

Background. This study examined whether alcohol abuse patients are characterized either by enhanced schematic processing of alcohol related cues or by an attentional bias towards the processing of alcohol cues. Method. Abstinent alcohol abusers (N = 25) and non-clinical control participants (N = 24) performed a dual task paradigm in which they had to make an odd/even decision to a centrally presented number while performing a peripherally presented lexical decision task. Stimuli on the lexical decision task comprised alcohol words, neutral words and non-words. In addition, participants completed an incidental recall task for the words presented in the lexical decision task. Results. It was found that, in the presence of alcohol related words, the performance of patients on the odd/even decision task was poorer than in the presence of other stimului. In addition, patients displayed slower lexical decision times for alcohol related words. Both groups displayed better recall for alcohol words than for other stimuli. Conclusions. These results are interpreted as supporting neither model of drug cravings. Rather, it is proposed that, in the presence of alcohol stimuli, alcohol abuse patients display a breakdown in the ability to focus attention.

Genetic modulation of the response bias towards facial displays of anger and happiness

Background: Investigating genetic modulation of emotion processing may contribute to the understanding of heritable mechanisms of emotional disorders. The aim of the present study was to test the effects of catechol- O-methyltransferase (COMT) val158met and serotonin-transporter-linked promoter region (5-HTTLPR) polymorphisms on facial emotion processing in healthy individuals. Methods: Two hundred and seventy five (167 female) participants were asked to complete a computerized facial affect recognition task, which involved four experimental conditions, each containing one type of emotional face (fearful, angry, sad or happy) intermixed with neutral faces. Participants were asked to indicate whether the face displayed an emotion or was neutral. The COMT-val158met and 5-HTTLPR polymorphisms were genotyped. Results: Met homozygotes (COMT) showed a stronger bias to perceive neutral faces as expressions of anger, compared with val homozygotes. However, the S-homozygotes (5-HTTLPR) showed a reduced bias to perceive neutral faces as expressions of happiness, compared to L-homozygotes. No interaction between 5-HTTLPR and COMT was found. Conclusions: These results add to the knowledge of individual differences in social cognition that are modulated via serotonergic and dopaminergic systems. This potentially could contribute to the understanding of the mechanisms of susceptibility to emotional disorders. © 2013 Elsevier Masson SAS.

Investigating G protein signalling bias at the glucagon-like peptide-1 receptor in yeast

Background and Purpose The glucagon-like peptide 1 (GLP-1) receptor performs an important role in glycaemic control, stimulating the release of insulin. It is an attractive target for treating type 2 diabetes. Recently, several reports of adverse side effects following prolonged use of GLP-1 receptor therapies have emerged: most likely due to an incomplete understanding of signalling complexities. Experimental Approach We describe the expression of the GLP-1 receptor in a panel of modified yeast strains that couple receptor activation to cell growth via single Gα/yeast chimeras. This assay enables the study of individual ligand-receptor G protein coupling preferences and the quantification of the effect of GLP-1 receptor ligands on G protein selectivity. Key Results The GLP-1 receptor functionally coupled to the chimeras representing the human Gαs, Gαi and Gαq subunits. Calculation of the dissociation constant for a receptor antagonist, exendin-3 revealed no significant difference between the two systems. We obtained previously unobserved differences in G protein signalling bias for clinically relevant therapeutic agents, liraglutide and exenatide; the latter displaying significant bias for the Gαi pathway. We extended the use of the system to investigate small-molecule allosteric compounds and the closely related glucagon receptor. Conclusions and Implications These results provide a better understanding of the molecular events involved in GLP-1 receptor pleiotropic signalling and establish the yeast platform as a robust tool to screen for more selective, efficacious compounds acting at this important class of receptors in the future. © 2014 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.