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.