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. 2018 Aug 8;9:3149. doi: 10.1038/s41467-018-05657-9

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© The Author(s) 2018

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. 1 — NAc somatostatin interneuron activity regulates cocaine-induced locomotor activity and reward. a AAV-DIO-EYFP or AAV-DIO-ChR2-EYFP were injected bilaterally into NAc of Sst-Cre mice 3 weeks prior to optogenetic stimulation or suppression, respectively, with the following parameters: Stimulation (473 nm, 20 Hz frequency, 1 burst of 10 pulses, 4 ms pulse width, every 10 s) or Suppression (473 nm, 20 Hz frequency, 1 burst of 20 pulses, 49 ms pulse width, every sec). b There is no difference between the locomotor activity of the three groups during habituation while the lasers remain off (repeated measures two-way ANOVA: no effect of activity F _(2,104) = 1.953. p = 0.147; n = 8,8,8) or day F_(4,104) = 0.3617. p = 0.9383; n = 8,8,8). c The activity of NAc somatostatin interneurons (EYFP control, Stimulation, or Suppression) controls the locomotor activity of mice after repeated cocaine injections. There is a significant effect of activity (repeated measures two-way ANOVA: significant effect of activity F_(2,21) = 5.647. p < 0.05; n = 8,8,8) and Day (Significant effect of Day F _(4,84) = 8.856. p < 0.001; n = 8,8,8). d Experimental design for unbiased CPP with optogenetics. Groups were counterbalanced to ensure that cocaine was paired evenly in both the gray and striped sides of the CPP chambers. e Stimulation of NAc somatostatin interneurons enhances cocaine CPP (Student's t-test: EYFP Pre-test vs EYFP Post-test, **p < 0.01; EYFP Pre-test mean = −16.50 ± 91.33 SEM vs EYFP Post-test mean = 376.4 ± 91.33 SEM (n = 8); CHR2-Stimulation Pre-test vs CHR2-Stimulation Post-Test, ****p < 0.0001 CHR2-Stimulation Pre-test mean = 51.00 ± 77.37 SEM vs CHR2-Stimulation Post-Test mean = 655.1 ± 53.93 SEM (n = 7); EYFP Post-test vs. CHR2-Stimulation Post-test, *p < 0.05 n = 8,7). f Cocaine CPP is blocked when NAc somatostatin interneurons are suppressed during training with cocaine. (Student’s t-test; AAV-DIO-EYFP Pre vs Post: **p < 0.01, EYFP Pre-test mean = −7.11 ± 66.2 SEM vs EYFP Post-test mean = 348.3 ± 90.41 SEM (n = 9)); AAV-DIO-CHR2 Pre vs Post: P > 0.05, n = 14). Data are represented as ± SEM