科研之友
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摘要
We observed modifications of behavior in rats with experimentally induced chronic aseptic inflammation of back tissues; these were increases in the levels of depressiveness and anxiety. Such shifts were manifested in increases in the time of immobilization in the forced swimming test and decreases in the time of stay of animals in open branches of the elevated X-like labyrinth. We also observed disorders in training for and realization of the conditioned active avoidance reaction (increases in the latency of this reaction and in the number of stimulation combinations necessary for providing its high stable level). Analysis of the effects of inflammation-derived products on neurons of layer V of the medial prefrontal cortex showed that chronic peripheral inflammation induces suppression of basal glutamatergic synaptic transmission combined with enhancement of the amplitudes of NMDA components of field EPSPs (fEPSPs) and decrease in the sensitivity of the latter to the influences of nonselective (ketamine) and selective with respect to NR2A subunits (zinc sulfate) blockers of NMDA receptors; the sensitivity to blockers of NR2B subunits (haloperidol) did not change. Induction of long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission were suppressed. In experiments on hippocampal slices, we observed weakening of the suppressive effect of serotonin (and not of those of buspirone and noradrenaline) on the amplitude of antidromic field APs of pyramidal neurons of the CA1 area. These facts demonstrate that the processes of serotonin (but not of noradrenaline) reuptake in varicosities of axons of monoaminergic neurons are intensified in inflammation. Considering the data obtained, we hypothesize that the increased level of depressiveness under conditions of chronic inflammation is determined, to a considerable extent, by enhanced functional activity of NMDA receptors and by weakening of serotonergic influences on cortical neurons. The increased anxiety level can be related to the above-mentioned weakening of serotonergic effects and/or to intensification of functional activity of high-threshold L-type calcium channels. Inflammation-related disorders of mnestic processes can result from a metaplastic shift of the threshold of induction of synaptic plasticity determined by the increase in functional activity of NMDA receptors and the above-mentioned calcium channels.
- 出版日期2013-5
