PMID- 35216236 OWN - NLM STAT- MEDLINE DCOM- 20220314 LR - 20220314 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 23 IP - 4 DP - 2022 Feb 14 TI - Alteration of Ethanol Reward by Prior Mephedrone Exposure: The Role of Age and Matrix Metalloproteinase-9 (MMP-9). LID - 10.3390/ijms23042122 [doi] LID - 2122 AB - Mephedrone, a synthetic cathinone, is widely abused by adolescents and young adults. The aim of this study was to determine: (i) whether prior mephedrone exposure would alter ethanol reward and (ii) whether age and matrix metalloproteinase-9 (MMP-9) are important in this regard. In our research, male Wistar rats at postnatal day 30 (PND30) received mephedrone at the dose of 10 mg/kg, i.p., 3 times a day for 7 days. To clarify the role of MMP-9 in the mephedrone effects, one mephedrone-treated group received minocycline, as an MMP-9 antagonist. Animals were then assigned to conditioned place preference (CPP) procedure at PND38 (adolescent) or at PND69 (adult). After the CPP test (PND48/79), expression of dopamine D1 receptors (D1R), Cav1.2 (a subtype of L-type calcium channels), and MMP-9 was quantified in the rat ventral striatum (vSTR). The influence of mephedrone administration on the N-methyl-D-aspartate glutamate receptors (NMDAR) subunits (GluN1, GluN2A, and GluN2B) was then assessed in the vSTR of adult rats (only). These results indicate that, in contrast with adolescent rats, adult rats with prior mephedrone administration appear to be more sensitive to the ethanol effect in the CPP test under the drug-free state. The mephedrone effect in adult rats was associated with upregulation of D1R, NMDAR/GluN2B, MMP-9, and Cav1.2 signaling. MMP-9 appears to contribute to these changes in proteins expression because minocycline pretreatment blocked mephedrone-evoked sensitivity to ethanol reward. Thus, our results suggest that prior mephedrone exposure differentially alters ethanol reward in adolescent and adult rats. FAU - Grochecki, Pawel AU - Grochecki P AD - Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4a, 20-093 Lublin, Poland. FAU - Smaga, Irena AU - Smaga I AUID- ORCID: 0000-0002-7783-8181 AD - Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland. FAU - Marszalek-Grabska, Marta AU - Marszalek-Grabska M AUID- ORCID: 0000-0002-2487-9131 AD - Department of Experimental and Clinical Pharmacology, Medical University, Jaczewskiego 8b, 20-090 Lublin, Poland. FAU - Lopatynska-Mazurek, Malgorzata AU - Lopatynska-Mazurek M AUID- ORCID: 0000-0001-5266-1968 AD - Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4a, 20-093 Lublin, Poland. FAU - Slowik, Tymoteusz AU - Slowik T AD - Experimental Medicine Center, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland. FAU - Gibula-Tarlowska, Ewa AU - Gibula-Tarlowska E AUID- ORCID: 0000-0001-7791-0633 AD - Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4a, 20-093 Lublin, Poland. FAU - Kedzierska, Ewa AU - Kedzierska E AD - Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4a, 20-093 Lublin, Poland. FAU - Listos, Joanna AU - Listos J AD - Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4a, 20-093 Lublin, Poland. FAU - Filip, Malgorzata AU - Filip M AUID- ORCID: 0000-0002-4321-7942 AD - Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland. FAU - Kotlinska, Jolanta H AU - Kotlinska JH AUID- ORCID: 0000-0002-4178-1515 AD - Department of Pharmacology and Pharmacodynamics, Medical University, Chodzki 4a, 20-093 Lublin, Poland. LA - eng GR - Grant UMO No. 2017/25/B/NZ7/01845/National Science Centre (NCN)/ GR - (DS 22/21)/Medical University of Lublin/ PT - Journal Article DEP - 20220214 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 3K9958V90M (Ethanol) RN - 44RAL3456C (Methamphetamine) RN - 8BA8T27317 (mephedrone) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) RN - EC 3.4.24.35 (Mmp9 protein, rat) SB - IM MH - Age Factors MH - Animals MH - Ethanol/*adverse effects MH - Male MH - Matrix Metalloproteinase 9/*metabolism MH - Methamphetamine/adverse effects/*analogs & derivatives MH - Rats MH - Rats, Wistar MH - Reward MH - Signal Transduction/drug effects MH - Ventral Striatum/drug effects/metabolism PMC - PMC8877998 OTO - NOTNLM OT - MMP-9 OT - age OT - conditioned place preference OT - ethanol OT - mephedrone OT - minocycline COIS- The authors declare no conflict of interest. EDAT- 2022/02/27 06:00 MHDA- 2022/03/15 06:00 PMCR- 2022/02/14 CRDT- 2022/02/26 01:07 PHST- 2022/01/20 00:00 [received] PHST- 2022/02/08 00:00 [revised] PHST- 2022/02/11 00:00 [accepted] PHST- 2022/02/26 01:07 [entrez] PHST- 2022/02/27 06:00 [pubmed] PHST- 2022/03/15 06:00 [medline] PHST- 2022/02/14 00:00 [pmc-release] AID - ijms23042122 [pii] AID - ijms-23-02122 [pii] AID - 10.3390/ijms23042122 [doi] PST - epublish SO - Int J Mol Sci. 2022 Feb 14;23(4):2122. doi: 10.3390/ijms23042122.