Neuropharmacology
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Randomized Controlled Trial
Effects of modafinil on non-verbal cognition, task enjoyment and creative thinking in healthy volunteers.
Modafinil, a putative cognitive enhancing drug, has previously been shown to improve performance of healthy volunteers as well as patients with attention deficit disorder and schizophrenia, mainly in tests of executive functions. The aim of this study was to investigate the effects of modafinil on non-verbal cognitive functions in healthy volunteers, with a particular focus on variations of cognitive load, measures of motivational factors and the effects on creative problem-solving. ⋯ Modafinil reliably enhanced task enjoyment and performance on several cognitive tests of planning and working memory, but did not improve paired associates learning. The findings confirm that modafinil can enhance aspects of highly demanding cognitive performance in non-sleep deprived individuals. This article is part of a Special Issue entitled 'Cognitive Enhancers'.
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Modafinil is a central nervous system wake promoting agent used for the treatment of excessive daytime sleeping. Its vigilance promoting properties and low abuse potential has intrigued the scientific community and has led to use it as a cognitive enhancer, before its neural functions were understood. Here, we review the effects of modafinil in human cognition and emotion and its specific actions on symptoms in patients with schizophrenia and whether these are consistently effective throughout the literature. ⋯ Other neurotransmitters were also activated by modafinil in various limbic brain areas, suggesting that the drug acts on these brain regions to influence emotional responses. These reviews seek to delineate the neuronal mechanisms by which modafinil affects cognitive and emotional function. This article is part of a Special Issue entitled 'Cognitive Enhancers'.
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Comparative Study
Matching biochemical and functional efficacies confirm ZIP as a potent competitive inhibitor of PKMζ in neurons.
PKMζ is an autonomously active, atypical protein kinase C (aPKC) isoform that is both necessary and sufficient for maintaining long-term potentiation (LTP) and long-term memory. The myristoylated ζ-pseudosubstrate peptide, ZIP, potently inhibits PKMζ biochemically in vitro, within cultured cells, and within neurons in hippocampal slices, and reverses LTP maintenance and erases long-term memory storage. A recent study (Wu-Zhang et al., 2012), however, suggested ZIP was not effective on a PKMζ fusion protein overexpressed in cultured cells. ⋯ However, here we show that staurosporine does not affect PDK1 phosphorylation of the endogenous PKMζ in hippocampal slices. Thus, the biochemical in vitro effects of PKMζ inhibitors correspond with their intracellular effects, and ZIP and chelerythrine, together with scrambled ZIP and staurosporine as controls, are effective tools to examine the function of PKMζ in neurons. This article is part of a Special Issue entitled 'Cognitive Enhancers'.
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GABA(B) receptor antagonists have been shown to have antidepressant-like properties in animal models and thus, could represent a novel approach for the treatment of depression. The neurobiological mechanisms underlying these effects are currently unknown. Adult hippocampal neurogenesis (the birth of new neurons) is thought to play a role in antidepressant drug action. ⋯ This topographical segregation concurs with the hypothesis that the ventral hippocampus is primarily involved in the regulation of stress and emotionality. Taken together, our data suggest that increased hippocampal cell proliferation is a plausible mechanism for the antidepressant-like effects of GABA(B) receptor antagonists following chronic but not acute treatments. Moreover, altered behavioural effects in the FST does not correlate with changes in neurogenesis.
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Diabetes is often associated with painful neuropathy. The current treatments are symptomatic and ineffective. Cannabinoids have been proposed as promising drugs for chronic pain treatment and its antinociceptive effect has already been related in nerve injury models of neuropathic pain, but little has been investigated in painful diabetic neuropathy models. ⋯ In Ngl rats, the antinociceptive effect of AM404 was prevented by AM251 or capsazepine only during first phase of the formalin test while in Dbt rats, this effect was blocked by pretreatment with AM251 (both phases) or AM630 (second phase). Taken together, these results demonstrated broad-spectrum antinociceptive properties of cannabinoids in a model of painful diabetic neuropathy. Peripheral activation of both cannabinoid receptors seems to mediate the antinociceptive effect of exogenous or endogenous anandamide.