Figure 3.

Cocaine degrades action-outcome memory

(A) Timeline. Cre-dependent Gq DREADDs were delivered to the VLO, and 4OHT induced Cre in cells active following unexpected non-reinforcement. Mice were then administered cocaine, followed by a washout period, and finally, Gq DREADDs+ cells were stimulated during a choice test. The rationale was that if cocaine weakened action memory representations, then stimulating these neurons may reinstate action flexibility. If cocaine instead ablated action memory, then Gq DREADDs should have no effects.

(B) Representative viral vector infusion. Gq DREADDs increased c-Fos, as expected. n = 6–8 mice/group. Scale bar = 100μm.

(C) Representative c-Fos+ puncta. Arrows indicating co-localization of c-Fos puncta and DREADD. Scale bar = 100 μm.

(D) Control mice favored a reinforced behavior, and cocaine obstructed response preference, as expected. Gq DREADDs stimulation, though, rescued flexible action in cocaine-exposed mice. Pie charts represent the number of mice/group that preferentially responded at the “reinforced” aperture.

(E) Response patterns when mice were next tested in omission.

(F) Response rates dropped considerably from the beginning to end of the session in control mice, reflected by large difference scores. Meanwhile, cocaine-alone mice responded similarly in the first and last time bins (scores ∼0), and Gq DREADDs boosted difference scores in cocaine-exposed mice.

(G) Line fits corresponding to e.

(H) Line fits with individual data points. The slope of the cocaine-alone group did not differ from 0, indicating no change across time. n = 6–8 mice/group. ∗p < 0.05 following t-test when comparing 2 groups at a single time point and ANOVA when comparing >2 groups and/or multiple time points. Simple linear regression analyses were also applied (bottom row). Bars and connected dots represent means (±SEMs if indicated), and unconnected dots represent individual mice.