Behavioural pharmacology
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Behavioural pharmacology · Feb 2008
Chronic stress in adulthood followed by intermittent stress impairs spatial memory and the survival of newborn hippocampal cells in aging animals: prevention by FGL, a peptide mimetic of neural cell adhesion molecule.
In this study, we examined whether chronic stress in adulthood can exert long-term effects on spatial-cognitive abilities and on the survival of newborn hippocampal cells in aging animals. Male Wistar rats were subjected to chronic unpredictable stress at midlife (12 months old) and then reexposed each week to a stress stimulus. When evaluated in the water maze at the early stages of aging (18 months old), chronic unpredictable stress accelerated spatial-cognitive decline, an effect that was accompanied by a reduction in the survival of newborn cells and in the number of adult granular cells in the hippocampus. ⋯ Administration of FGL, a peptide mimetic of neural cell adhesion molecule, during the 4 weeks of continuous stress not only prevented the deleterious effects of chronic stress on spatial memory, but also reduced the survival of the newly generated hippocampal cells in aging animals. FGL treatment did not, however, prevent the decrease in the total number of granular neurons that resulted from prolonged exposure to stress. These findings suggest that the development of new drugs that mimic neural cell adhesion molecule activity might be of therapeutic relevance to treat stress-induced cognitive impairment.
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Behavioural pharmacology · Feb 2008
Pharmacologic investigation of the mechanism underlying cold allodynia using a new cold plate procedure in rats with chronic constriction injuries.
Cold allodynia is a frequent clinical symptom of patients with neuropathic pain. Despite numerous studies of cold allodynia, using animal models of neuropathic pain, little is known about its underlying mechanisms. This study was performed to establish a method for the pharmacologic evaluation of cold allodynia using several analgesics in a chronic constriction injury (CCI) rat model of neuropathic pain. ⋯ Under this condition, both the sodium channel blocker mexiletine (10 and 30 mg/kg, subcutaneously) and the calcium channel alpha2delta subunit blocker pregabalin (30 and 100 mg/kg, orally) significantly suppressed cold allodynia. Additionally, both resiniferatoxin (0.3 mg/kg, subcutaneously), an ultrapotent analog of capsaicin that desensitizes C fibers, and the VR1 channel antagonist N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2-yl) tetrahydropyrazine-1(2H)-carboxamide (10 and 30 mg/kg, orally) significantly prolonged the paw withdrawal latency. In conclusion, our data suggest that the activation of C fibers mediates cold allodynia.