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. Author manuscript; available in PMC: 2022 Feb 2.
Published in final edited form as: Addict Biol. 2021 Aug 25;27(1):e13097. doi: 10.1111/adb.13097

Figure 3.

Figure 3.

Inhibition and activation of the prelimbic (PL)-nucleus accumbens (NA)core circuit and methamphetamine seeking in response to drug cues. A. Experimental timeline for experiments 1–4. B. Active and inactive lever responding (left axis) and meth infusions (right axis) over 15 daily 2 hr sessions. Self-administration data is combined for all experiments represented in D-G. The individual graphs per experiment are disaggregated by sex and depicted in Supplemental Figure 4. C. Active and inactive lever responding over 10 daily extinction (Ext) sessions. Extinction data is combined for all experiments represented in D-G. The individual graphs per experiment are disaggregated by sex and depicted in Supplemental Figure 4. D. Active lever presses during extinction (calculated as the mean of the last 2 extinction sessions) and in response to presentation of meth associated cues following an injection of vehicle, 3 or 10 mg/kg CNO. All groups increased active lever presses relative to extinction in rats with DIO-hM4Di in the PL. However, lever responding following 10 mg/kg clozapine-N-oxide (CNO) was significantly decreased relative to vehicle and 3 mg/kg CNO. E. Active lever presses following abstinence in response to an injection of vehicle or 10 mg/kg CNO. In rats with DIO-hM4Di in the PL, lever responding decreased following an injection of 10 mg/kg CNO relative to VEHICLE following re-exposure to the meth context after abstinence. F. Active lever presses during extinction and in response to presentation of meth associated cues following an injection of vehicle or 10 mg/kg CNO in rats with DIO hM3Dq in the PL. Both test conditions increased responding relative to extinction. G. Active lever presses during extinction and in response to presentation of meth associated cues following an injection of vehicle, 3 or 10 mg/kg CNO. Rats with DIO-mCherry in the PL rather than the DREADD increased lever responding relative to extinction across all test conditions. (G) The schematic represents the extent of mCherry expression in the anteroposterior representation of the prefrontal cortex.

*Significant difference from 10 mg/kg CNO.

#Significant difference from extinction.