British journal of pharmacology
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Activation of cannabinoid (CB) receptors decreases nociceptive transmission in inflammatory or neuropathic pain states. However, the effects of CB receptor agonists in post-operative pain remain to be investigated. Here, we characterized the anti-allodynic effects of WIN 55,212-2 (WIN) in a rat model of post-operative pain. ⋯ Both CB(1) and CB(2) receptors were involved in the peripheral anti-allodynic effect of systemic WIN in a pre-clinical model of post-operative pain. In contrast, the centrally mediated anti-allodynic activity of systemic WIN is mostly due to the activation of CB(1) but not CB(2) receptors at both the spinal cord and brain levels. However, the increased potency of WIN following i.c.v. administration suggests that its main site of action is at CB(1) receptors in the brain.
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Comparative Study
Intrathecal injection of the neurosteroid, DHEAS, produces mechanical allodynia in mice: involvement of spinal sigma-1 and GABA receptors.
The neurosteroid, dehydroepiandrosterone sulphate (DHEAS) and its non-sulphated form, DHEA, are considered as crucial endogenous modulators of a number of important physiological events. Evidence suggests that DHEAS and DHEA modulate central nervous system-related functions by activating sigma-1 receptors and/or allosterically inhibiting gamma-aminobutyric acid receptor type A (GABA(A)) receptors. As both the sigma-1 receptor and the GABA(A) receptor play important roles in spinal pain transmission, the present study was designed to examine whether intrathecally injected DHEAS or DHEA affect nociceptive signalling at the spinal cord level. ⋯ These findings indicate that i.t. injection of DHEAS produces mechanical allodynia and that the development of this mechanical allodynia is mediated by sigma-1 and GABA(A) receptors. The findings of this study raise several interesting questions for further investigations into the mechanisms underlying neurosteroid modulation of spinal pain transmission.
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Adult neurogenesis occurs throughout life in the subgranular zone and the dentate gyrus of the hippocampus. Deficient neurogenesis may be responsible for deficient hippocampal functions in neurodegenerative disorders such as Alzheimer's disease (AD). T-817MA [1-{3-[2-(1-Benzothiophen-5-yl)ethoxy] propyl}-3-azetidinol maleate] is a newly synthesized agent for AD treatment with neuroprotective effects against toxicity from amyloid-beta peptide (Abeta) and actions promoting neurite outgrowth in vitro. Furthermore, systemic administration of T-817MA ameliorated cognitive dysfunctions caused by neurodegeneration in a rat model of AD, induced by intracerebroventricular (i.c.v.) infusion of Abeta. The present study investigated quantitative relationships between spatial memory performance in Abeta-infused rats and hippocampal neurogenesis, and the effects of T-817MA on neuronal proliferation in vivo. ⋯ These results suggest that defective hippocampal neurogenesis is a new target for AD treatment. The neurotrophic compound T-817MA increased hippocampal neurogenesis in an AD model and might be useful for treatment of AD patients.