Neuropharmacology
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In this study, we investigated the involvement of the interaction between sigma receptors and the nitric oxide/cyclic GMP pathway in short term memory in mice, assessed through spontaneous alternation behavior in a Y-maze. N(G)-Nitro-L-arginine methyl ester and 7-nitro indazole, both nitric oxide synthase inhibitors, impaired the spontaneous alternation behavior. These impairments were attenuated by (+) SKF 10,047 and (+) pentazocine, sigma(1) receptor agonists. ⋯ The suppressive effects of N(G)-nitro-L-arginine methyl ester on the cyclic GMP levels were reversed by co-treatment with (+) SKF 10,047, but the decline in nitric oxide synthase activity was not. These results suggest that the nitric oxide/cyclic GMP pathway in the hippocampus is responsible for spontaneous alternation behavior in a Y-maze. Further, the ameliorating effects of (+) SKF 10,047 on the impairment of spontaneous alternation behavior may be mediated through activation of guanylate cyclase, but not nitric oxide synthase in the hippocampus of mice.
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Low-frequency stimulation of primary afferent Adelta-fibers can induce long-term depression of synaptic transmission in rat superficial spinal dorsal horn. Here, we have identified another form of long-term depression in superficial spinal dorsal horn neurons that is induced by specific group I but not group II metabotropic glutamate receptor (mGluR) agonists. Synaptic strength between Adelta-fibers and dorsal horn neurons was examined by intracellular recordings in a spinal cord-dorsal root slice preparation from young rat. ⋯ The phospholipase C inhibitor U73122 stereoselectively blocked the induction of long-term depression without affecting acute synaptic inhibition. This study demonstrates that, in the spinal cord, direct activation of group I mGluRs that are coupled to phospholipase C through pertussis toxin-insensitive G-proteins induces a long-term depression of synaptic strength. This may be relevant to the processing of sensory information in the spinal cord, including nociception.