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Dynorphin\u2010mediated signalling within the striatum is associated with negative affect following cocaine withdrawal and stress\u2010induced cocaine seeking. Here, we used a trace conditioning procedure to first establish the optimum parameters to capture this transient cocaine negative affective state in wild\u2010type mice, and then we investigated striatal opioid peptides as a substrate mediating cocaine conditioned place avoidance (CPA). Previous reports indicate that trace conditioning, where drug administration occurs after removal from the conditioning chamber, results in CPA to ethanol, nicotine and amphetamine. We tested different cocaine doses, conditioning session lengths and apparatus types to determine which combination yields the best cocaine CPA. Cocaine CPA was moderately larger at the highest cocaine dose (25\u2009mg\/kg), but this did not generalize across apparatus types and the effect was transient; thus, data were collapsed across all parameters. Cocaine conditioning scores were variable but also became more polarized across conditioning, with approximately equal proportions developing preference and avoidance. We then correlated cocaine CPA with striatal gene expression levels of the opioid peptides enkephalin (\n                    <jats:italic>Penk<\/jats:italic>\n                    ) and dynorphin (\n                    <jats:italic>Pdyn<\/jats:italic>\n                    ) using qPCR. Cocaine CPA was correlated with low\n                    <jats:italic>Pdyn<\/jats:italic>\n                    levels and a low\n                    <jats:italic>Pdyn<\/jats:italic>\n                    :\n                    <jats:italic>Penk<\/jats:italic>\n                    ratio in the ventral, but not dorsal, striatum. Consistent with this, mice with higher striatal\n                    <jats:italic>Pdyn<\/jats:italic>\n                    relative to\n                    <jats:italic>Penk<\/jats:italic>\n                    were more resistant to developing cocaine CPA compared with littermate controls. This approach revealed a subset of subjects sensitive to the aversive state immediately following cocaine administration. Our findings suggest that striatal dynorphin has opposing roles in mediating the aversion associated with acute cocaine intoxication versus cocaine withdrawal.\n                  <\/jats:p>","DOI":"10.1111\/adb.70055","type":"journal-article","created":{"date-parts":[[2025,7,6]],"date-time":"2025-07-06T21:24:20Z","timestamp":1751837060000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Shifted Balance Between Ventral Striatal Prodynorphin and Proenkephalin Biases Development of Cocaine Place Avoidance"],"prefix":"10.1111","volume":"30","author":[{"given":"Am\u00e9lia","family":"Nicot","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Waggoner Center for Alcohol and Addiction Research The University of Texas at Austin  Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavankumar","family":"Yecham","sequence":"additional","affiliation":[{"name":"Department of Psychology Brain Health Institute, Rutgers, The State University of New Jersey  Piscataway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilana","family":"Serin","sequence":"additional","affiliation":[{"name":"Department of Neurology Dell Medical School, The University of Texas at Austin  Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4609-6787","authenticated-orcid":false,"given":"David\u00a0J.","family":"Barker","sequence":"additional","affiliation":[{"name":"Department of Psychology Brain Health Institute, Rutgers, The State University of New Jersey  Piscataway New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7489-9977","authenticated-orcid":false,"given":"Lauren\u00a0K.","family":"Dobbs","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Waggoner Center for Alcohol and Addiction Research The University of Texas at Austin  Austin Texas USA"},{"name":"Department of Neurology Dell Medical School, The University of Texas at Austin  Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajad.13502"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.15242"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213\u2010013\u20103309\u20100"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091\u20103057(99)00109\u20104"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1986.01800020013003"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3634\u201012.2013"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002130000499"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a115166"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2006.02.005"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0376\u20108716(96)01324\u20105"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091\u20103057(92)90203\u2010r"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166\u20104328(94)90008\u20106"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091\u20103057(92)90386\u2010t"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02244244"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2003.11.009"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091\u20103057(96)00300\u20100"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0708\u201020.2020"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1847\u201020.2021"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(98)00060-4"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1369\u20101600.2007.00070.x"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0149\u20107634(94)00021\u2010R"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02245166"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111440"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2014.02.021"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3758\/BF03199022"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00210847"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(90)90209-Z"},{"key":"e_1_2_11_29_1","volume-title":"Learning and Memory","author":"Purdy J. 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