The international journal of neuropsychopharmacology
-
Int. J. Neuropsychopharmacol. · Sep 2014
Protein kinase Mζ is involved in the modulatory effect of fluoxetine on hippocampal neurogenesis in vitro.
The efficacy of chronic selective serotonin reuptake inhibitors (SSRIs) on depression is paralleled by the recovery of deficits in hippocampal neurogenesis related to sustained stress and elevated glucocorticoids. Previous studies have shown that atypical protein kinase C (aPKC) is implicated in the regulation of neurogenesis and the antidepressant response. Whether the specific aPKC isoforms (PKCζ, PKMζ and PKCι) are involved in SSRI-induced hippocampal neurogenesis and the underlying mechanisms is unknown. ⋯ Fluoxetine significantly increased PKMζ expression in hippocampal NSCs in a 5-hydroxytryptamine-1A (5-HT1A) receptor-dependent manner in both the absence and presence of dexamethasone. The PKMζ peptide blocker ZIP and MEK inhibitor U0126 significantly inhibited the increase in extracellular signal-regulated kinase 1/2 and cyclic adenosine monophosphate response element binding protein phosphorylation in the mitogen-activated protein kinase (MAPK) pathway and hippocampal NSC neurogenesis in response to fluoxetine and the 5-HT1A receptor agonist 8-OH DPAT. Collectively, our results suggest that the SSRI fluoxetine increases hippocampal NSC neurogenesis via a PKMζ-mediated mechanism that links 5-HT1A receptor activation with the phosphorylation of the downstream MAPK signaling pathway.
-
Int. J. Neuropsychopharmacol. · Sep 2014
Effects of brief pulse and ultrabrief pulse electroconvulsive stimulation on rodent brain and behaviour in the corticosterone model of depression.
Brief pulse electroconvulsive therapy (BP ECT; pulse width 0.5-1.5 ms) is the most effective treatment available for severe depression. However, its use is associated with side-effects. The stimulus in ultrabrief pulse ECT (UBP ECT; pulse width 0.25-0.3 ms) is more physiological and has been reported to be associated with less cognitive side-effects, but its antidepressant effectiveness is not yet well established. ⋯ Both forms of ECS also induced significant increases in BDNF protein (p < 0.01) expression in the hippocampus. BP ECS (p < 0.05) but not UBP ECS induced a significant increase in GFAP levels in the hippocampus and frontal cortex. Overall, UBP ECS effectively induced antidepressant-related behavioural and molecular responses in the corticosterone supplementation model, providing the first preclinical data on the potential role of this form of ECS to treat a depression phenotype related to elevated corticosterone.
-
Int. J. Neuropsychopharmacol. · Sep 2014
Cognitive related electrophysiological changes induced by non-invasive cortical electrical stimulation in crack-cocaine addiction.
Prefrontal dysfunction is a hallmark in drug addiction, yet interventions exploring modulation of prefrontal cortex function in drug addiction have not been fully investigated with regard to physiological alterations. We tested the hypothesis that non-invasive prefrontal stimulation would change neural activity in crack-cocaine addiction, investigating the effects of transcranial Direct Current Stimulation (tDCS) of Dorsolateral Prefrontal Cortex (DLPFC) induced cortical excitability modulation on the visual P3 Event Related Potentials (ERP) component under neutral and drug cue exposition in crack-cocaine addicts. Thirteen crack-cocaine users were randomly distributed to receive five applications (once a day, every other day) of bilateral (left cathodal/right anodal) tDCS (20 min, 2 mA, 35 cm2) or sham tDCS over the DLPFC. ⋯ This effect was opposite to what was observed in the sham-tDCS group. In contrast, repetitive tDCS increased current density not only in the DLPFC, but also in a wider array of prefrontal areas, including presumably the frontopolar cortex (FPC) orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC), when subjects were visualizing crack-related cues. Thus, single and repetitive application of tDCS can impact cognitive processing of neutral and especially crack-related visual cues in prefrontal areas, which may be of importance for treatment of crack-cocaine addiction.
-
Int. J. Neuropsychopharmacol. · Sep 2014
The phosphodiesterase-4 inhibitor rolipram attenuates heroin-seeking behavior induced by cues or heroin priming in rats.
Inhibition of phosphodiesterase-4 (PDE4), an enzyme that specifically hydrolyzes cyclic adenosine monophosphate (cAMP) increases intracellular cAMP/cAMP-response element binding protein (CREB) signaling. Activation of this signaling is considered as an important compensatory response that decreases motivational properties of drugs of abuse. However, it is not known whether PDE4 is involved in heroin seeking. ⋯ Finally, the effects of rolipram on heroin-seeking behavior were correlated with the increases in expression of phosphorylated CREB in the nucleus accumbens. The study demonstrated that rolipram inhibited heroin reward and heroin-seeking behavior. The results suggest that PDE4 plays an essential role in mediating heroin seeking and that PDE4 inhibitors may be used as a potential pharmacotherapeutic approach for heroin addiction.