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. 2021 Jan 8;12:182. doi: 10.1038/s41467-020-20526-0

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — a Baseline: Rats freely explore chamber for 20 min. Conditioning: Rats receive three pairings/side of saline and 10 mg/kg cocaine, i.p. (for conditioned place preference (CPP) validation) or vehicle (VEH) + cocaine and CNO (5 mg/kg, i.p.) (or LED light; 20 Hz, 20 ms pulses) + cocaine (modified CPP paradigm) over 3 days (2 conditioning sessions/day). CPP test: 24 h post-conditioning, rats freely explore chamber for 20 min. b–i Bar and whisker plots where bars represent the mean ± SEM difference in time spent on a side between the post-conditioning CPP test and the Baseline pretest. b Validation: Rats spent significantly more time on the cocaine-paired side (orange) than the saline-paired side, indicating a CPP to cocaine. N = 4. c IT hM₄Di: There was no difference in the time spent on the CNO + cocaine-paired side (purple) compared to the VEH + cocaine-paired side, indicating that IT inhibition does not modulate cocaine reward. N = 6. d PT hM₄Di: Rats spent significantly more time on the CNO + cocaine-paired side (green) than the VEH + cocaine-paired side, indicating that PT inhibition enhances cocaine reward. N = 6. e PT ChR2: Rats spent significantly less time on the light + cocaine-paired side (green) compared to cocaine alone, indicating that PT stimulation decreases cocaine reward. N = 4. f There was no difference in the time spent when rats received VEH or CNO (green) prior to saline on each side, indicating that PT inhibition alone is not reinforcing. N = 5. g There was no difference in the time spent when rats received light + saline (green) compared to saline alone, indicating that PT stimulation alone is not aversive. N = 4. h Validation: Rats spent significantly more time on the M&M candy-paired side (orange) compared to the food-paired side, indicating a CPP to a hedonic natural reward. N = 9. i PT hM₄Di: There was no difference in the time spent on the CNO + M&M-paired side (green) compared to the VEH + M&M-paired side, indicating that PT inhibition does not modulate the rewarding properties of a natural reinforcer. N = 6, *p < 0.05, **p < 0.01, paired t-test.