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

Fig. 1. Alcohol-induced infralimbic mGluR2 deficit leads to impaired ASST performance.

Fig. 1.

(A) Scheme of chronic alcohol-vapor exposure leading to stable blood alcohol concentrations and significantly increased somatic withdrawal scores. After 3 weeks of abstinence, batches of animals were used either for spine density analysis, attentional set-shifting test (ASST), or lentiviral infralimbic mGluR2 rescue. (B) Scheme of ASST, where rats have to make serial discriminative choices based on olfactory or tactile cues/dimensions. ASST performance of alcohol-dependent [postdependent (PD), n = 14, black squares] rats need significantly more trials to criterion in the IDS and EDS subtasks compared to control rats (n = 15, white circles). (C) Scheme of the delay discounting task (DDT). The graph below represents the percentage preference for the high reward against the delay of the high reward in time. Alcohol-dependent rats have a steeper curve (means ± SEM) compared to controls. (D) Schematic representation of genomic location of premature stop codon in P rats (50). (E) Alcohol-naïve Indiana P rats (n = 12, black triangles) do not differ in IDS/EDS tasks compared to Indiana NP rats (n = 12, white triangles). (F) Schematic representation of lentiviral constructs. Lenti-mGluR2 expresses Grm2 and cop green fluorescent protein (copGFP) under control of elongation factor 1-alpha (EF1α) promoter. Lenti-control only expresses copGFP under EF1α control. ENV; Epstein-Barr virus derived vector, cPPT; central polypurine tract, WPRE; Woodchuck posttranscriptional regulatory element. (G) Injection placements are represented by black circles. Injection sites were verified within the infralimbic cortex from +3.2 to +2.2 mm anterior to bregma (85). (H) ASST performance of PD rats injected with either lenti-mGluR2 (n = 16, red squares) or lenti-control (n = 16, black squares) into the infralimbic cortex. In the EDS component of the task, no difference was observed between control and virally infected PD rats. However, in the IDS component, lenti-mGluR2–injected animals overall needed significantly fewer trials to criterion. IDS, intradimensional shift; EDS, extradimensional shift; *P < 0.05, **P < 0.01, and ***P < 0.001.