Progress in neuro-psychopharmacology & biological psychiatry
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Oct 2012
Sildenafil influences the anticonvulsant activity of vigabatrin and gabapentin in the timed pentylenetetrazole infusion test in mice.
Sildenafil, a selective phosphodiesterase 5 (PDE5) inhibitor, has recently been reported to affect convulsant activity in some animal models of seizures and epilepsy. Moreover, its influence on the protective activity of some antiepileptic drugs (AEDs) was also noted. The aim of the present study was to investigate the effect of sildenafil on the anticonvulsant potential of gabapentin (GBP) and vigabatrin (VGB) in the timed intravenous (i.v.) pentylenetetrazole (PTZ) test in mice. ⋯ The studied AEDs and their combinations with sildenafil did not produce any changes in the motor coordination, long-term memory and muscular strength in mice. Sildenafil did not influence total brain and free plasma concentrations of GBP and VGB. Interactions between the studied AEDs and sildenafil were pharmacodynamic in nature and for that reason they are worthy of consideration in the clinical practice.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Oct 2012
Chronic restraint stress causes anxiety- and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex.
Stress and the resulting increase in glucocorticoid levels have been implicated in the pathophysiology of depressive disorders. We investigated the effects of chronic restraint stress (CRS: 6 hours × 28 days) on anxiety- and depression-like behaviors in rats and on the possible changes in glucocorticoid receptor (GR) expression as well as brain-derived neurotrophic factor (BDNF)-dependent neural function in the prefrontal cortex (PFC). We observed significant reductions in body weight gain, food intake and sucrose preference from 1 week after the onset of CRS. ⋯ Basal glutamate concentrations in PFC acute slice which were measured by high performance liquid chromatography were not influenced by CRS. However, BDNF-induced glutamate release was attenuated after CRS. These results suggest that reduced GR expression and altered BDNF function may be involved in chronic stress-induced anxiety--and depression-like behaviors.