Onsite QTc interval screening for patients in methadone maintenance treatment.

To improve the electrocardiogram screening process and early detection of patients at high risk for cardiac arrhythmias, the authors created a model in their clinic where they provided an onsite electrocardiogram screening that might be feasible and practical. The authors then performed a retrospective chart review to access the efficacy and feasibility of their new onsite procedure in identifying methadone maintained patients at high risk for cardiac arrhythmias. Records from all patients who are currently or had previously been maintained on methadone in the methadone maintenance program at the Atlanta VA Medical Center between 2002 and 2009 were evaluated.

An essential role for DeltaFosB in the nucleus accumbens in morphine action.

The transcription factor DeltaFosB is induced in the nucleus accumbens (NAc) and dorsal striatum by the repeated administration of drugs of abuse. Here, we investigated the role of DeltaFosB in the NAc in behavioral responses to opiates. We achieved overexpression of DeltaFosB by using a bitransgenic mouse line that inducibly expresses the protein in the NAc and dorsal striatum and by using viral-mediated gene transfer to specifically express the protein in the NAc.

Regulation of CRE-mediated transcription in mouse brain by amphetamine.

Previous work has demonstrated that acute and chronic administration of amphetamine causes phosphorylation of the transcription factor CREB, the cAMP response element (CRE) binding protein, in striatum, a brain region important for the behavioral actions of the drug. To determine whether such phosphorylation is associated with changes in CREB transcriptional activity, we mapped beta-galactosidase (beta-gal) expression in a CRE-LacZ transgenic mouse, in which the beta-gal reporter is downstream of CRE sequences, following acute or chronic amphetamine administration. We found that acute amphetamine induced beta-gal expression in a relatively small number of brain regions, including nucleus accumbens (ventral striatum), amygdala, ventral tegmental area, and locus coeruleus.

Regional and cellular mapping of cAMP response element-mediated transcription during naltrexone-precipitated morphine withdrawal.

Chronic opiate exposure is associated with upregulation of the cAMP signaling pathway and the transcription factor cAMP response element-binding protein in the locus ceruleus (LC) and certain other brain areas. To determine whether these adaptations ultimately affect transcription mediated by the cAMP response element (CRE), we induced morphine dependence in CRE-LacZ transgenic mice and performed a regional and cellular mapping of beta-galactosidase (beta-gal) expression during naltrexone-precipitated withdrawal. Consistent with our model of opiate dependence, beta-gal expression increased in the LC, but decreased in the lateral ventral tegmental area (VTA) and dorsal raphe nucleus (DRN).