Guanfacine

2PLU experiments were performed in normal ACSF supplemented with MNI-glutamate (2.5 mM) and D-serine (10 μM). To isolate AMPAR-mediated currents in voltage clamp experiments, we added tetrodotoxin (TTX) (1 μM) to block sodium channels, picrotoxin (50 μM) to block GABA_A receptors, CGP55845 (3 μM) to block GABA_B receptors, and 3-(2-Carboxypiperazin-4-yl) propyl-1-phosphonic acid (CPP) (10 μM) to block NMDA-type glutamate receptors to the ACSF. To isolate NMDAR-mediated currents, we modified our original ACSF to contain 0 mM Mg and 3 mM Ca2+ and included TTX (1 μM), picrotoxin (50 μM), CGP55845 (3 μM), and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX) (10 μM) to block AMPA-type glutamate receptors. To activate α2 adrenergic receptors we used 40 μM guanfacine (Tocris). The selective GABA_B receptor agonist baclofen (Tocris), a drug primarily used as a muscle relaxant, approved by the US Food and Drug Administration, was applied at 5 μM. Both G-protein coupled receptor (GPCR) agonists were applied 5–7 minutes prior to data collection and remained in the bath for the duration of the experiment, but typically no longer than 20 minutes to avoid receptor desensitization. All compounds and salts were from Tocris and Sigma, respectively.