The international journal of neuropsychopharmacology
-
Recently, we created a family of engineered G protein-coupled receptors (GPCRs) called DREADD (designer receptors exclusively activated by designer drugs) which can precisely control three major GPCR signaling pathways (Gq, Gi, and Gs). DREADD technology has been successfully applied in a variety of in vivo studies to control GPCR signaling, and here we describe recent advances of DREADD technology and discuss its potential application in drug discovery, gene therapy, and tissue engineering.
-
Int. J. Neuropsychopharmacol. · Dec 2014
The mood stabilizer lithium potentiates the antidepressant-like effects and ameliorates oxidative stress induced by acute ketamine in a mouse model of stress.
Evidence suggests that mammalian target of rapamycin activation mediates ketamine's rapid but transient antidepressant effects and that glycogen synthase kinase-3β inhibits this pathway. However, ketamine has associated psychotomimetic effects and a high risk of abuse. The mood stabilizer lithium is a glycogen synthase kinase-3 inhibitor with strong antisuicidal properties. Here, we used a mouse stress model to investigate whether adjunct lithium treatment would potentiate ketamine's antidepressant-like effects. ⋯ Our results suggest a novel therapeutic strategy and justify the use of lithium in patients who benefit from ketamine.
-
Int. J. Neuropsychopharmacol. · Dec 2014
Preclinical to clinical translation of CNS transporter occupancy of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor.
Monoamine reuptake inhibitors exhibit unique clinical profiles that reflect distinct engagement of the central nervous system (CNS) transporters. ⋯ These data establish the CNS penetration and transporter profile of TD-9855 and inform the selection of potential doses for future clinical evaluation.
-
Int. J. Neuropsychopharmacol. · Nov 2014
Randomized Controlled TrialA randomized controlled trial of targeted prefrontal cortex modulation with tDCS in patients with alcohol dependence.
Preliminary small studies have shown that transcranial direct current stimulation (tDCS) reduces craving in alcoholic subjects. It is unclear whether tDCS also leads to changes in clinically meaningful outcomes for alcohol dependence in a properly powered phase II randomized clinical trial. We aimed to investigate whether repetitive tDCS changes the risk of alcohol use relapse in severe alcoholics from outpatient services. ⋯ No differences with regard to changes on scores of craving, frontal function, global mental status, depressive or anxiety symptoms were observed between groups. However, subjects from the tDCS group improved with regard to their overall perception of quality of life (p=0.02), and increased their scores in the environment domain (p=0.04) after treatment. Bilateral tDCS over dlPFC reduces relapse probability in severe alcoholic subjects and results in improved perception of quality of life.
-
Int. J. Neuropsychopharmacol. · Nov 2014
Neurocognitive performance and serial intravenous subanesthetic ketamine in treatment-resistant depression.
The N-methyl-D-aspartate glutamate receptor antagonist ketamine has demonstrated rapid antidepressant effects in treatment-resistant depression (TRD). However, evaluation of ketamine's neurocognitive aspects in TRD has started to be explored. This study aims to (1) examine baseline neurocognitive performance and change in severity of depressive symptoms through six ketamine infusions, (2) examine the neurocognitive effects after completion of serial infusions and whether changes were associated to relapse to depression. ⋯ However, neurocognitive changes were accounted for by improvement in the severity of depressive symptom. The acute neurocognitive effect after completion of repeated infusions was not associated with the likelihood of subsequent relapse during follow-up. Our findings suggest a potential baseline neurocognitive predictor of ketamine response and the apparently lack of short-term neurocognitive impairment after completion of six ketamine infusions in TRD.