Progress in neuro-psychopharmacology & biological psychiatry
-
Prog. Neuropsychopharmacol. Biol. Psychiatry · Dec 2010
Comparative StudyPostoperative cognitive deficits and neuroinflammation in the hippocampus triggered by surgical trauma are exacerbated in aged rats.
Postoperative cognitive dysfunction (POCD) is characterized by the progressive deterioration of intellectual/cognitive function following surgery. It has been suggested that the senile brain, which characteristically expresses higher levels of central proinflammatory cytokines, interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α, is more susceptible to additional insult following surgery. The authors of this study investigated the expression of central cytokines IL-1β, IL-6 and TNF-α and hippocampal glial cell activation in aged and adult rats following partial hepatectomy. ⋯ Immunohistochemistry assay further showed more hippocampal glial cell activation in aged rats compared to that in adults. Overall, these findings suggest that surgical trauma, rather than anesthesia, resulted in cognitive function impairment potentiated by aging. Hippocampal pro-inflammatory cytokines and glial cell activation might mediate trauma-induced POCD.
-
Prog. Neuropsychopharmacol. Biol. Psychiatry · Dec 2010
Comparative StudyDifferential regulation of neurotrophin S100B and BDNF in two rat models of depression.
Several clinical studies have demonstrated that serum brain-derived neurotrophic factor (BDNF) levels are decreased and serum S100B levels are increased in patients with major depression. In this study, we investigated whether these findings could be replicated in animal models of depression. We measured BDNF and S100B protein levels in the serum, prefrontal cortex, striatum and hippocampus of rats in models of depression, i.e., olfactory bulbectomy (OBX) and chronic unpredictable stress (CUS) models. ⋯ No significant correlation was found between serum and regional brain S100B/BDNF levels. Our findings suggest that both of these animal models of depression, in which similar serum S100B level changes to those in depressed patients were observed, could be used as valid models to explore the role of S100B underlying major depression. Neither serum S100B nor BDNF levels reflect their levels in the brain, and changes in their levels in patients with neuropsychiatric diseases should be interpreted cautiously.
-
Prog. Neuropsychopharmacol. Biol. Psychiatry · Dec 2010
Comparative StudyThe high-affinity nAChR partial agonists varenicline and sazetidine-A exhibit reinforcing properties in rats.
Varenicline (Chantix®, Champix®) is a nicotinic acetylcholine receptor (nAChR) partial agonist clinically approved for smoking cessation, yet its potential abuse liability properties have not been fully characterized. The nAChR ligand sazetidine-A has been reported as a selective full or partial agonist at α4β2* nAChR subtypes in in vitro studies. In the present studies, varenicline, sazetidine-A and nicotine exhibited inverted U-shaped dose-response functions under fixed-ratio (peak responding at 30, 60 and 10-30 μg/kg/inf, respectively) or progressive-ratio (peak responding at 30-60, 30-100 and 30 μg/kg/inf, respectively) schedules in rats trained to self-administer nicotine. ⋯ Nonetheless, self-administration and re-acquisition of varenicline and sazetidine-A were less robust than nicotine. Thus, partial activation of α4β2* nAChRs by varenicline or sazetidine-A is sufficient to mimic the DS and reinforcing properties of nicotine in nicotine-experienced rats, although the reinforcing properties of partial agonists are diminished in nicotine-naïve rats. Future studies should assess nicotine withdrawal measures in animals chronically exposed to varenicline or sazetidine-A.
-
Prog. Neuropsychopharmacol. Biol. Psychiatry · Aug 2010
The wide variability of perospirone metabolism and the effect of perospirone on prolactin in psychiatric patients.
Perospirone was developed in Japan and is used for the treatment of schizophrenia and related illnesses. The authors investigated the relationship between the dosage of perospirone and the plasma levels of perospirone and its active metabolite, ID15036, and also evaluated the impact of the plasma concentrations of perospirone and ID15036 on the plasma prolactin level to examine whether perospirone or ID15036 affected the dopamine D(2) blockade, in psychiatric patients treated with perospirone. ⋯ The plasma levels of ID15036 may have a greater impact on the dopamine D(2) blockade than perospirone in patients treated with perospirone.
-
Prog. Neuropsychopharmacol. Biol. Psychiatry · Aug 2010
Depressive-like behaviors alterations induced by intranigral MPTP, 6-OHDA, LPS and rotenone models of Parkinson's disease are predominantly associated with serotonin and dopamine.
Depression is a frequently encountered non-motor feature of Parkinson's disease (PD) and it can have a significant impact on patient's quality of life. Considering the differential pathophysiology of depression in PD, it prompts the idea that a degenerated nigrostriatal system plays a role in depressive-like behaviors, whilst animal models of PD are employed. Therefore, we addressed the question of whether dopamine (DA) depletion, promoted by the neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 6-hydroxydopamine (6-OHDA), lipopolysaccharide (LPS) and rotenone are able to induce depressive-like behaviors and neurotransmitters alterations similarly that encountered in PD. ⋯ Notably, strong correlations were detected among the groups when 5-HT and DA were correlated with swimming (r=+0.97; P=0.001) and immobility (r=-0.90; P=0.012), respectively. Our data indicate that MPTP, 6-OHDA and rotenone, but not LPS were able to produce depressive-like behaviors accompanied primarily by hippocampal 5-HT reductions. Moreover, DA and 5-HT strongly correlated with "emotional" impairments suggesting an important participation of these neurotransmitters in anhedonia and behavioral despair after nigral lesions promoted by the neurotoxins.