Progress in neuro-psychopharmacology & biological psychiatry
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Jun 2009
Intracisternal administration of COX inhibitors attenuates mechanical allodynia following compression of the trigeminal ganglion in rats.
The purpose of the present study was to investigate the role of central cyclooxygenase (COX) pathways in the modulation of mechanical allodynia following compression of the left trigeminal ganglion. Experiments were carried out on male Sprague-Dawley rats mounted onto a stereotaxic frame under anesthesia. For compression, a 4% agar solution (10 microl) was injected into the trigeminal ganglion. ⋯ Intracisternal administration of indomethacin, a non-selective COX inhibitor, SC-560, a selective COX-1 inhibitor, or NS-398, a selective COX-2 inhibitor, significantly inhibited mechanical allodynia. The individual anti-allodynic effects of the three COX inhibitors persisted for 6 h and returned to pretreatment values within 24 h. Based on these results, the blockade of central COX pathways may comprise a potential new therapeutic tool for the treatment of trigeminal ganglion compression-induced nociception.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Apr 2009
Distinct effects of acute and chronic sleep loss on DNA damage in rats.
The aim of this investigation was to evaluate genetic damage induced in male rats by experimental sleep loss for short-term (24 and 96 h) and long-term (21 days) intervals, as well as their respective recovery periods in peripheral blood, brain, liver and heart tissue by the single cell gel (comet) assay. Rats were paradoxically deprived of sleep (PSD) by the platform technique for 24 or 96 h, or chronically sleep-restricted (SR) for 21 days. We also sought to verify the time course of their recovery after 24 h of rebound sleep. ⋯ Corticosterone concentrations were increased after PSD (24 and 96 h) relative to control rats, whereas these levels were unaffected in the SR group. Collectively, these findings reveal that sleep loss was able to induce genetic damage in blood and brain cells, especially following acute exposure. Since DNA damage is an important step in events leading to genomic instability, this study represents a relevant contribution to the understanding of the potential health risks associated with sleep deprivation.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Apr 2009
Clinical TrialAugmentation of antidepressants with perospirone for treatment-resistant major depressive disorder.
We examined the efficacy and tolerability of perospirone, a dopamine D2 and 5-HT2A receptor antagonist and a partial 5-HT1A receptor agonist, in the augmentation of antidepressant treatment of partially responding and nonresponding patients with major depressive disorder. Twelve patients with major depressive disorder and an incomplete or no response to different kinds of antidepressants (selective serotonin reuptake inhibitor, milnacipran, or sulpride) monotherapy or polytherapy for 8 weeks or more were treated with perospirone augmentation in an eight-week, open-label study. Data were gathered from July 2006 to March 2008. ⋯ The discontinuation rate after 8 weeks of treatment was zero. These findings suggest that perospirone may be an effective augmentation strategy for improving therapeutic response in patients with treatment-resistant major depressive disorder when administered in combination with standard antidepressant therapy. Based on this clinical evidence, a double-blind, placebo-controlled trial is warranted.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Apr 2009
TPH2 -703G/T SNP may have important effect on susceptibility to suicidal behavior in major depression.
Serotonergic system-related genes can be good candidate genes for both major depressive disorder (MDD) and suicidal behavior. In this study, we aimed to investigate the association of serotonin 2A receptor gene -1438A/G SNP (HTR2A -1438A/G), tryptophan hydroxylase 2 gene -703G/T SNP (TPH2 -703G/T) and serotonin 1A receptor C-1019G (HTR1A C-1019G) with suicidal behavior. ⋯ Our results suggest that TPH2 -703G/T SNP may have an important effect on susceptibility to suicidal behavior. Furthermore, an increased frequency of G allele of TPH2 SNP may be associated with elevated suicidal behavior itself rather than with the diagnosis of major depression and may increase risk of suicidality, independent of diagnosis.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Mar 2009
Sex differences in corticolimbic dopamine and serotonin systems in the rat and the effect of postnatal handling.
Stress-related psychopathology is particularly prevalent in women, although the neurobiological reason(s) for this are unclear. Dopamine (DA) and serotonin (5-HT) systems however, are known to play important adaptive roles in stress and emotion regulation. The aims of the present study included examination of sex differences in stress-related behaviour and neuroendocrine function as well as post mortem neurochemistry, with the main hypothesis that corticolimbic DA and 5-HT systems would show greater functional activity in males than females. ⋯ In contrast, males had higher levels of the DA metabolite DOPAC or DOPAC/DA ratios than females in all five regions and higher levels of the 5-HT metabolite 5-HIAA or 5-HIAA/5-HT ratios in vmPFC, amygdala and insula, suggesting greater neurotransmitter utilization in males. Moreover, handling treatment induced a significant male-specific upregulation of 5-HT metabolism in all regions except n. accumbens. Given the adaptive role of 5-HT and DAergic neurotransmission in stress and emotion regulation, the intrinsic sex differences we report in the functional status of these systems across conditions, may be highly relevant to the differential vulnerability to disorders of stress and emotion regulation.