Progress in neuro-psychopharmacology & biological psychiatry
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Jul 2012
ReviewEffects induced by cannabinoids on monoaminergic systems in the brain and their implications for psychiatric disorders.
The endocannabinoid system and CB(1) receptors participate in the control of emotional behavior and mood through a functional coupling with the classic monoaminergic systems. In general, the acute stimulation of CB(1) receptors increases the activity (spontaneous firing rate) of noradrenergic (NE), serotonergic (5-HT) and dopaminergic (DA) neurons as well as the synthesis and/or release of the corresponding neurotransmitter in specific brain regions. Notably, the antagonist/inverse agonist rimonabant (SR141617A) can decrease the basal activity of NE and 5-HT neurons, suggesting a tonic/constitutive regulation of these neuronal systems by endocannabinoids acting at CB(1) receptors. ⋯ CB(1) receptor desensitization may alter the direct and/or indirect effects of cannabinoid drugs modulating the functionality of monoaminergic systems. The sustained activation of monoaminergic neurons by cannabinoid drugs can also be related to changes in the function of presynaptic inhibitory α(2)-adrenoceptors or 5-HT(1A) receptors (autoreceptors and heteroreceptors), whose sensitivity is downregulated or upregulated upon chronic CB(1) agonist exposure. The functional interactions between endocannabinoids and monoaminergic systems in the brain indicate a potential role for CB(1) receptor signaling in the neurobiology of various psychiatric disorders, including major depression and schizophrenia as the major syndromes.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Jul 2012
ReviewInvolvement of descending serotonergic and noradrenergic pathways in CB1 receptor-mediated antinociception.
Cannabinoids produce antinociceptive and antihyperalgesic effects mainly through activation of the inhibitory CB1 receptors. The demonstration that antinociceptive effects of systemic cannabinoids are significantly diminished following surgical dorsolateral funiculus lesion provides evidence that supraspinal sites and descending pain modulatory pathways play crucial roles in systemic cannabinoid analgesia. ⋯ We will then describe the recent evidence of the involvement of descending serotonergic and noradrenergic pathways in CB1 receptor-mediated antinociception. This review will provide evidences that systemically administered cannabinoids reinforce the descending serotonergic and noradrenergic pathways to produce acute antinociceptive effects via spinal 5-HT7, 5-HT2A and alpha-2 adrenoceptors activation.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Aug 2011
ReviewThe use of the zebrafish model in stress research.
The study of the causes and mechanisms underlying psychiatric disorders requires the use of non-human models for the test of scientific hypotheses as well as for use in pre-clinical drug screening and discovery. This review argues in favor of the use of zebrafish as a novel animal model to study the impact of early (stressful) experiences on the development of differential stress phenotypes in later life. This phenomenon is evolutionary conserved among several vertebrate species and has relevance to the etiology of psychiatric disorders. ⋯ The zebrafish model helps resolve these issues. Here we present a conceptual framework for the use of zebrafish in stress research and psychiatry by addressing three specific domains of application: 1) stress research, 2) human disease mechanisms, and 3) drug discovery. We also present novel methodologies associated with the development of the zebrafish stress model and discuss how such methodologies can contribute to remove the main bottleneck in the field of drug discovery.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Jun 2011
Review Meta AnalysisStructural and functional neuroimaging studies of the suicidal brain.
Suicidality is a major challenge for today's health care. Evidence suggests that there are differences in cognitive functioning of suicidal patients but the knowledge about the underlying neurobiology is limited. Brain imaging offers the advantage of a non-invasive in vivo direct estimation of detailed brain structure, regional brain functioning and estimation of molecular processes in the brain. ⋯ We did not find studies measuring the binding potential of the noradrenalin or gamma amino butyric acid transporter or receptor in suicidal subjects. Several reports have suggested abnormalities of GABA neurotransmission in depression. During our literature search, we have focused on neuroimaging studies in suicidal populations, but in the absence of evidence in the literature on this group or when further collateral evidence is appropriate, this overview expands to results in impulsive aggressive or in depressed subjects.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Jun 2011
ReviewMelatonin agonists in primary insomnia and depression-associated insomnia: are they superior to sedative-hypnotics?
Current pharmacological treatment of insomnia involves the use of sedative-hypnotic benzodiazepine and non-benzodiazepine drugs. Although benzodiazepines improve sleep, their multiple adverse effects hamper their application. Adverse effects include impairment of memory and cognitive functions, next-day hangover and dependence. ⋯ The novel antidepressant agomelatine, a dual action agent with affinity for melatonin MT1 and MT2 receptors and 5-HT2c antagonistic properties, constitutes a new approach to the treatment of major depressive disorders. Agomelatine ameliorates the symptoms of depression and improves the quality and efficiency of sleep. Taken together, the evidence indicates that MT1/MT2 receptor agonists like ramelteon or agomelatine may be valuable pharmacological tools for insomnia and for depression-associated insomnia.