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In this animal model of depression, spine loss probably involves a weakening of the interaction between pre\u2010 and postsynaptic cell adhesion molecules, such as N\u2010cadherin, followed by disruption of the cytoskeleton. N\u2010cadherin, in concert with catenin, stabilizes the cytoskeleton through Rho\u2010family GTPases. Via their effector LIM kinase (LIMK), RhoA and ras\u2010related C3 botulinum toxin substrate 1 (RAC) GTPases phosphorylate and inhibit cofilin, an actin\u2010depolymerizing molecule, favoring spine growth. Additionally, RhoA, through Rho kinase (ROCK), inactivates myosin phosphatase through phosphorylation of the myosin\u2010binding subunit (MYPT1), producing actomyosin contraction and probable spine loss. Some micro\u2010RNAs negatively control the translation of specific mRNAs involved in Rho GTPase signaling. For example, miR\u2010138 indirectly activates RhoA, and miR\u2010134 reduces LIMK1 levels, resulting in spine shrinkage; in contrast, miR\u2010132 activates RAC1, promoting spine formation. We evaluated whether N\u2010cadherin\/\u03b2\u2010catenin and Rho signaling is sensitive to chronic restraint stress. Stressed rats exhibit anhedonia, impaired associative learning, and immobility in the forced swim test and reduction in N\u2010cadherin levels but not \u03b2\u2010catenin in the hippocampus. We observed a reduction in spine number in the apical dendrites of CA1 pyramidal neurons, with no effect on the levels of miR\u2010132 or miR\u2010134. Although the stress did not modify the RAC\u2013LIMK\u2013cofilin signaling pathway, we observed increased phospho\u2010MYPT1 levels, probably mediated by RhoA\u2013ROCK activation. Furthermore, chronic stress raises the levels of miR\u2010138 in accordance with the observed activation of the RhoA\u2013ROCK pathway. 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