Progress in neuro-psychopharmacology & biological psychiatry
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Dec 2008
Randomized Controlled Trial Clinical TrialA 12-week, double-blind, placebo-controlled trial of donepezil adjunctive treatment to risperidone in chronic and stable schizophrenia.
There is considerable incentive to develop new treatment strategies that effectively target cognitive deficits in schizophrenia. One of the theoretically promising novel treatment candidates is acetylcholinesterase inhibitors that increase the synaptic levels of cholinergic, nicotinic, and muscarinic receptor activity. The purpose of this study was to assess the efficacy of donepezil as an adjuvant agent in the treatment of chronic schizophrenia in particular for cognitive impairments. ⋯ The donepezil group had significantly greater improvement in the negative symptoms over the 12-week trial. There were no differences between the donepezil and placebo groups on any neurocognitive assessments at endpoint (week 12). The present study indicates donepezil as a potential adjunctive treatment strategy for negative symptoms of chronic schizophrenia.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Dec 2008
Involvement of L-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of tramadol in the rat forced swimming test.
Tramadol is a centrally acting analgesic which is used mainly for the treatment of moderate or severe pain. It is a synthetic opioid in the aminocyclohexanol group that binds weakly to micro-opioid receptors. Since it has been suggested that both opioid and monoaminergic systems play a role in depressive disorders, tramadol has been studied in the forced swimming test (FST). ⋯ Pretreatment of animals with methylene blue (3.75 mg/kg i.p., an inhibitor of NO synthase and soluble guanylate cyclase - sGC) or (1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one) (ODQ, 2 mg/kg, i.p., a specific inhibitor of sGC) significantly caused a synergistic effect with a sub-effective dose of tramadol (5 mg/kg, p.o.) in the FST. In the present study, different doses of tramadol and the combination with the L-arginine-NO-cGMP pathway modulators had no effect on the locomotor activity of rats in the open-field test. Thus, our findings suggest that the acute administration of tramadol produces antidepressant-like effect in the rat FST by a mechanism that involves the inhibition of L-arginine-NO-cGMP pathway.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Aug 2008
Secretion of S100B, an astrocyte-derived neurotrophic protein, is stimulated by fluoxetine via a mechanism independent of serotonin.
S100B is a calcium-binding protein, produced and secreted by astrocytes, which has a putative paracrine neurotrophic activity. Clinical studies have suggested that peripheral elevation of this protein is positively correlated with a therapeutic antidepressant response, particularly to selective serotonin reuptake inhibitors (SSRIs); however, the mechanism underlying this response remains unclear. ⋯ Moreover, we found that serotonin (possibly via the 5HT1A receptor) reduces S100B secretion and antagonizes the effect of fluoxetine on S100B secretion. These data reinforce the effect of fluoxetine, independently of serotonin and serotonin receptors, suggesting a putative role for S100B in depressive disorders and suggesting that other molecular targets may be relevant for antidepressant activity.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Jul 2008
ReviewTobacco/nicotine and endogenous brain opioids.
Smoking is a major public health problem with devastating health consequences. Although many cigarette smokers are able to quit, equal numbers of others cannot. ⋯ These include: especially dopamine, but also norepinephrine, 5-hydroxytryptamine, acetylcholine, endogenous opioids, gamma-aminobutyric acid (GABA), glutamate, and endocannabinoids. The present review examines the limited contribution of the endogenous opioid system to the complex effects of nicotine/tobacco smoking.