Behavioural brain research
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Endoplasmic reticulum (ER) stress has been postulated to play a crucial role in the pathophysiology of cerebral ischemic/reperfusion (I/R) injury and diabetes. Diabetes is a major risk factor and also common amongst the people who suffer from stroke. In this study, we have investigated the neuroprotective potential of sodium 4-phenylbutyrate (SPB; 30-300mg/kg), a chemical chaperone by targeting ER stress in a rat model of transient focal cerebral ischemia associated with comorbid type 2 diabetes. ⋯ The neuroprotection observed with SPB was independent of its effect on cerebral blood flow and blood glucose. In conclusion, this study demonstrates the neuroprotective effect of SPB owing to amelioration of ER stress and DNA fragmentation. It also suggest that targeting ER stress might offer a promising therapeutic approach and benefits against ischemic stroke associated with comorbid type 2 diabetes.
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In the present study, we investigated effects of intra-central amygdala (intra-CeA) administrations of a β1-receptor agonist and antagonist, isoprenaline (isoproterenol) and atenolol respectively, on state-dependent memory induced by a cannabioid agonist, WIN55,212-2. This study used a step-through inhibitory avoidance task to assess memory in male Wistar rats. The results showed that post-training intra-CeA administrations of different doses of WIN55,212-2 (0.01, 0.05, 0.1 and 0.25μg/rat) decreased memory as revealed by a decrease in memory retrieval on the test day. ⋯ The results also showed that pre-test intra-CeA administrations of atenolol (0.01, 0.05 and 0.1μg/rat) alone had no effect, but at dose of 0.1μg/rat disrupted state-dependent memory induced by WIN55,212-2. Moreover, the improving effect of isoprenaline (0.025μg/rat) on retrieval of state-dependent memory induced by WIN55,212-2 (0.1μg/rat) was prevented by intra-CeA co-injections of atenolol. Taken together, our results suggest that the CeA may be potentially critical for state-dependent memory induced by WIN55,212-2 and the β1-noradrenergic receptor mechanism(s) interact with the cannabinergic system in the modulation of this kind of memory in the CeA.
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Clinical and preclinical data reported that ascorbic acid has antidepressant properties. The present study was designed to investigate the participation of l-arginine-NO-cGMP pathway in the antidepressant-like effect of ascorbic acid in the tail suspension test (TST) in mice. ⋯ None of the results in the TST appears to be due to a nonspecific locomotor effect. Our findings provide evidence that the effect of ascorbic acid in the TST involve an interaction with NMDA receptors and l-arginine-NO-cGMP pathway, contributing to the understanding of the mechanisms underlying the antidepressant-like effect of this vitamin.