Fig. 4: BDNF in vlOFC-to-DLS circuit moderates habitual alcohol seeking.

a Experimental timeline: mice underwent 7 weeks of IA20%2BC alcohol in their home cage (Supplementary Table 1). Mice were then trained to operant self-administer 20% alcohol for four weeks on an FR1 schedule followed by an initial habitual alcohol seeking training using random interval (RI) training schedule. Mice were pseudo-randomly assigned to two groups. Control group received bilateral infusions of AAV2-DIO-mCherry in the vlOFC and AAVretro-Cre-GFP in the DLS. The second group received AAV2-DIO-BDNF-mCherry in the vlOFC and AAVretro-Cre-GFP in the DLS. Three weeks after surgery, RI training was resumed followed by contingency degradation testing. Mice then underwent extinction. Lever presses were recorded during the first extinction session and during a reinstatement session. b–d Operant self-administration. Average of active lever presses (b), rewards (c) frequency of active lever presses (d) during the operant training sessions 3 weeks after surgery. e Contingency degradation test: non degraded (ND) and degraded (D). During ND sessions, rewards were delivered on an RI schedule. During D sessions, alcohol rewards were delivered at a rate equal to the average of the last week of training. f, g Average of active lever presses (f) during ND and D testing sessions in RI schedule of reinforcement of AAV-DIO-mCherry infected and AAV-DIO-BDNF-mCherry infected mice. g Cumutative active lever presses of AAV-DIO-mCherry infected and AAV-DIO-BDNF-mCherry infected mice during the 2 hr degradation session. Extinction: the total number of lever presses (h), cumulative number of lever presses (i), port entries (j), and the latency to the first active lever press (k) were recorded. Reacquisition: the total number of lever presses (l), cumulative number of lever presses (m), port entries (n), and the latency to the first active lever press (o) were recorded. Data represented as mean ± SEM. *p < 0.05. n = 5 per group.