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The enduring effects of an adolescent social stressor on synaptic density, part II: Poststress reversal of synaptic loss in the cortex by adinazolam and MK‐801
Author(s) -
Leussis Melanie P.,
Lawson Katherine,
Stone Kimberly,
Andersen Susan L.
Publication year - 2008
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20483
Subject(s) - synaptophysin , infralimbic cortex , prefrontal cortex , glutamatergic , hippocampus , neuroscience , nucleus accumbens , synaptic plasticity , hippocampal formation , tianeptine , endocrinology , psychology , glutamate receptor , medicine , central nervous system , antidepressant , cognition , immunohistochemistry , receptor
Experience programs synaptic development to match the needs of the environment. This process depends on the nature and timing of the experience. Exposure to stress during adolescence selectively reduces synaptic density in the prefrontal cortex (a later maturing region), while sparing hippocampal synapses (an earlier maturing region). To determine whether the anatomical effects of an adolescent social stressor in rats endures into adulthood and are reversible, male subjects were isolation or group housed between days 30 and 35 and then treated with vehicle, adinazolam, MK‐801, or tianeptine between days 40 and 55. At day 60, immunohistochemistry revealed a 13.5% ± 5.3% reduction in synaptophysin in the infralimbic cortex and cingulate gyrus in isolation‐housed subjects. MK‐801 and adinazolam restored cortical synaptic density to within 2% of group‐housed values, suggesting that the synaptic loss induced by stress during adolescence is modulated through reduced glutamatergic activity directly by NMDA antagonism or indirectly by enhancing GABAergic activity. Tianeptine did not modulate adolescent stress effects in the prefrontal cortex. None of these drugs increased cortical synaptophysin in group‐housed controls. Increased synaptophysin was observed in the group‐housed condition in the hippocampus, striatum, and nucleus accumbens following drug exposure. Although stress did not decrease synaptic density in these regions, drug exposure failed to increase synaptic density when compared with the controls. Taken together, stress‐induced changes in cortical, but not hippocampal, synaptic density initiated during adolescence endure into adulthood. These cortical changes can be reversed through a reduction of glutamatergic activity, but not serotonin augmentation. © 2007 Wiley‐Liss, Inc. Synapse 62:185–192, 2008.