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Chunk #11 — RESULTS — Reduced AcbC Crem expression mediates impulsive action

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Ventral striatal regulation of CREM mediates impulsive action and drug addiction vulnerability.
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We next over-expressed Crem in the AcbC of SHRs and evaluated ITD and heroin SA to determine this gene’s potential causal relationship to impulsivity and related behavior. For ITD, HSV-Crem-Gfp or HSV-Gfp (Gfp alone) was bilaterally infused into the AcbC one day before the start of testing (Supplementary Fig. 4a). Compared to control, HSV-Crem-Gfp infusion elevated Crem expression (t7=2.56, p=0.038, Fig. 2c) but did not alter choice for large reward (Fig. 2d, Supplementary Fig. 4b) or locomotor activity (Supplementary Fig. 4e). Instead, these animals exhibited lower intra-delay L1 responses as the delay increased (F5,50=2.40, p=0.05, Fig. 2e) while neither intra-delay L5 pressing (F5,50=2.32, p=0.06, Supplementary Fig. 4c) nor L1 pressing during the time-out period (F1,10=0.52, p=0.49, Supplementary Fig. 4d) differed between groups. These data show that AcbC Crem specifically reduced L1 responses during the delay period and suggest an association with impulsive action, not impulsive choice, compulsivity or general hyperactivity. For heroin SA, HSV-Crem-Gfp or HSV-Gfp was bilaterally infused into the AcbC of a different cohort of animals the day before the first session. Over-expression did not impact responses on