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. 2019 May 17;9(5):113. doi: 10.3390/brainsci9050113

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© 2019 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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The α2A-AR agonist guanfacine can strengthen PFC connectivity and protect the PFC from stress. (A) Chronic restraint stress causes loss of apical distal spines from layer II/III prelimbic PFC pyramidal cells in rats. Daily pre-treatment with guanfacine prevents spine loss and protects working memory function. CN = control, ST = chronic restraint stress, VEH = vehicle, GFC = guanfacine. * or ** significantly different from vehicle control; † or †† significantly different from vehicle stress at p < 0.05 or 0.01 levels, respectively. Figure 4A adapted from [93]. (B) Schematic diagram showing that guanfacine stimulation of α2A-AR on spines strengthens connectivity and protects PFC from stress by inhibiting cAMP-calcium-K⁺ channel signaling.