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. 2021 Nov 17;7(47):eabh2399. doi: 10.1126/sciadv.abh2399

Fig. 4. Effect of mGluR2 knockdown in infralimbic and corticostriatal projection neurons on impairments of executive functions and cue-induced reinstatement of alcohol-seeking behavior.

Fig. 4.

(A) Scheme of ASST, where rats have to make serial discriminative choices based on olfactory or tactile cues/dimensions. ASST performance of CamKII-Cre rats injected with either control AAV (n = 9, white bars) or Cre-dependent knockdown AAV (n = 9, black bars) into the infralimbic mPFC. The knockdown animals needed significantly more trials to criterion in the EDS subtask and overall needed more trials to criterion as compared to control animals. **P < 0.01. (B) Experimental timeline of alcohol-seeking behavior: All animals underwent alcohol self-administration (SA) and extinction (EXT) training, followed by a cue-induced reinstatement session of alcohol seeking (RE1). Following stereotaxic AAV injection (control AAV or mGluR2 knockdown AAV, n = 9 per group) and a recovery period of 4 weeks, the animals were tested during a second cue-induced reinstatement session (RE2). (C) Active and inactive operant responses of CamKII-Cre rats before control (white bars, n = 7) and knockdown (black bars, n = 7). AAV injection (two control and two knockdown animals had to be excluded from analysis because they failed to reach the criterion for successful cue-induced reinstatement of alcohol seeking, which was >10 active lever presses). There was no significant difference between the groups during BL, EXT, and cue-induced RE1 responding. (D) Performance of CamKII-Cre rats injected with control or Cre-induced mGluR2 knockdown AAV. Data were normalized to RE1 performance (before AAV injection). There was a significant difference between the groups in RE2 and a significant difference in the knockdown group between RE1 (before AAV injection) and RE2. *P < 0.05, **P < 0.01 indicate significant differences between control, knockdown/alcohol-dependent (PD) rats, and between RE2 and RE1, respectively.