{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:31:11Z","timestamp":1792161071993,"version":"4.4.0"},"reference-count":86,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T00:00:00Z","timestamp":1674000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre (NCN)","award":["UMO No. 2017\/25\/B\/NZ7\/01845"],"award-info":[{"award-number":["UMO No. 2017\/25\/B\/NZ7\/01845"]}]},{"name":"National Science Centre (NCN)","award":["DS 22\/21"],"award-info":[{"award-number":["DS 22\/21"]}]},{"name":"Medical University of Lublin","award":["UMO No. 2017\/25\/B\/NZ7\/01845"],"award-info":[{"award-number":["UMO No. 2017\/25\/B\/NZ7\/01845"]}]},{"name":"Medical University of Lublin","award":["DS 22\/21"],"award-info":[{"award-number":["DS 22\/21"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Treatment of Post-Traumatic Stress Disorder (PTSD) is complicated by the presence of drug use disorder comorbidity. Here, we examine whether conditioned fear (PTSD model) modifies the rewarding effect of mephedrone and if repeated mephedrone injections have impact on trauma-related behaviors (fear sensitization, extinction, and recall of the fear reaction). We also analyzed whether these trauma-induced changes were associated with exacerbation in metalloproteinase-9 (MMP-9) and the GluN2A and GluN2B subunits of N-methyl-D-aspartate (NMDA) glutamate receptor expression in such brain structures as the hippocampus and basolateral amygdala. Male adolescent rats underwent trauma exposure (1.5 mA footshock), followed 7 days later by a conditioned place preference training with mephedrone. Next, the post-conditioning test was performed. Fear sensitization, conditioned fear, anxiety-like behavior, extinction acquisition and relapse were then assessed to evaluate behavioral changes. MMP-9, GluN2A and GluN2B were subsequently measured. Trauma-exposed rats subjected to mephedrone treatment acquired a strong place preference and exhibited impairment in fear extinction and reinstatement. Mephedrone had no effect on trauma-induced MMP-9 level in the basolateral amygdala, but decreased it in the hippocampus. GluN2B expression was decreased in the hippocampus, but increased in the basolateral amygdala of mephedrone-treated stressed rats. These data suggest that the modification of the hippocampus and basolateral amygdala due to mephedrone use can induce fear memory impairment and drug seeking behavior in adolescent male rats.<\/jats:p>","DOI":"10.3390\/ijms24031941","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T02:51:37Z","timestamp":1674096697000},"page":"1941","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Impact of Mephedrone on Fear Memory in Adolescent Rats: Involvement of Matrix Metalloproteinase-9 (MMP-9) and N-Methyl-D-aspartate (NMDA) Receptor"],"prefix":"10.3390","volume":"24","author":[{"given":"Pawel","family":"Grochecki","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7783-8181","authenticated-orcid":false,"given":"Irena","family":"Smaga","sequence":"additional","affiliation":[{"name":"Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Wydra","sequence":"additional","affiliation":[{"name":"Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2487-9131","authenticated-orcid":false,"given":"Marta","family":"Marszalek-Grabska","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, Medical University, Jaczewskiego 8B, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tymoteusz","family":"Slowik","sequence":"additional","affiliation":[{"name":"Experimental Medicine Center, Medical University, Jaczewskiego 8, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Kedzierska","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Listos","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7791-0633","authenticated-orcid":false,"given":"Ewa","family":"Gibula-Tarlowska","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4321-7942","authenticated-orcid":false,"given":"Malgorzata","family":"Filip","sequence":"additional","affiliation":[{"name":"Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4178-1515","authenticated-orcid":false,"given":"Jolanta H.","family":"Kotlinska","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4A, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"h6161","DOI":"10.1136\/bmj.h6161","article-title":"Post-traumatic stress disorder","volume":"351","author":"Bisson","year":"2015","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.psc.2009.06.001","article-title":"Posttraumatic stress disorder and stress-related disorders","volume":"32","author":"Shalev","year":"2009","journal-title":"Psychiatr. 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