Brain research bulletin
-
Brain research bulletin · Oct 2015
The spinal antinociceptive mechanism determined by systemic administration of BD1047 in zymosan-induced hyperalgesia in rats.
Although sigma-1 receptor (Sig-1R) antagonists have a potential antinociceptive effect in inflammatory diseases, the precise mechanism is not fully understood. The present study was aimed to elucidate the role of spinal neurons and microglia in the anti-nociceptive mechanism of BD1047 (a prototypical Sig-1R antagonist) using an inflammatory pain model based on intraplantar injection of zymosan. Oral pretreatment with BD1047 dose-dependently reduced zymosan-induced thermal and mechanical hyperalgesia as well as spinal neuronal activation including increased immunoreactivity of Fos, protein kinase C (PKC) and 'PKC-dependent phosphorylation of the NMDA receptor subunit 1' (pNR1). ⋯ In the spinal cord section, Sig-1R immunoreactivity was exclusively distributed in both spinal dorsal horn neurons and central endings of unmyelinated primary afferent fibers but not in glia. Intrathecal injection of BD1047 alleviated zymosan-induced hyperalgesia up to the level of oral administration. Taken together, our data imply that antinociceptive effect induced by oral treatment with BD1047 may be mediated, at least in part, by the inhibition of neuronal and microglial activation in the spinal cord triggered by inflammatory conditions.
-
Brain research bulletin · Oct 2015
Enriched environment improves synaptic plasticity and cognitive deficiency in chronic cerebral hypoperfused rats.
Recent studies have indicated that environmental enrichment (EE) increases the sensorial and social stimulations and leads to strengthened plastic changes in the brain. In models of chronic cerebral hypoperfusion, the ability of an EE to restore the cognition depends on hippocampal synaptic plasticity. The mechanisms for this effect have not, however, been adequately studied. ⋯ In addition, conditions of the environment did not have any effect on baseline synaptic transmission and presynaptic plasticity, but housing the animals in EE rescued the impairment of LTP induction induced by 2-VO. These results suggest that EE ameliorates the LTP and spatial memory impairment induced by 2-VO. Our data indicated that the LTP recovery by EE in the rat models of 2-VO is probably mediated by post-synaptic mechanisms.