PMID- 33242543 OWN - NLM STAT- MEDLINE DCOM- 20210514 LR - 20210605 IS - 1873-7544 (Electronic) IS - 0306-4522 (Print) IS - 0306-4522 (Linking) VI - 452 DP - 2021 Jan 1 TI - Sex- and Brain Region-specific Changes in Gene Expression in Male and Female Rats as Consequences of Methamphetamine Self-administration and Abstinence. PG - 265-279 LID - S0306-4522(20)30742-9 [pii] LID - 10.1016/j.neuroscience.2020.11.025 [doi] AB - Sex differences in METH use exist among human METH users and in animal models of METH addiction. Herein, we tried to identify potential differences in gene expression between female and male rats after Methamphetamine self-administration (METH SA). Rats were trained to self-administer METH using two 3-hours daily sessions for 20 days. Cue-induced drug seeking was measured on withdrawal days 3 (WD3) and 30 (WD30). Rats were euthanized twenty-four hours after WD30. Prefrontal cortex (PFC) and hippocampus (HIP) were dissected to measure mRNA expression. Both female and male rats increased their METH intake and showed increased METH seeking during withdrawal. Female had higher basal level expression of hypocretin receptor 1 (Hcrtr1) and prodynorphin (Pdyn) mRNAs in the PFC and HIP. Basal corticotropin releasing hormone receptor 1 (Crhr1), Crh receptor 2 (Crhr2), hypocretin receptor 2 (Hcrtr2) and opioid receptor kappa 1 (Oprk1) mRNA levels were higher in the PFC of females. Male rats had higher basal levels of Crh and Crhr1 in HIP. METH SA was associated with increased Crh and Crhr1 in the HIP of both sexes and Crhr2 only in female HIP. Importantly, increased Crh and Crhr1 mRNA levels correlated positively with incubation of METH craving in both sexes, supporting their potential involvement, in part, in the regulation of this behavioral phenomenon. When taken together, our results identified sexual dimorphic baseline differences in rats. We also detected dimorphic responses in animals that had self-administered METH. These observations highlight the importance of understanding the molecular neurobiology of sex differences when therapeutic interventions are planned against METH addiction. CI - Published by Elsevier Ltd. FAU - Daiwile, Atul P AU - Daiwile AP AD - Molecular Neuropsychiatry Research Branch, NIDA Intramural Research Program, Baltimore, MD 21224, United States. FAU - Jayanthi, Subramaniam AU - Jayanthi S AD - Molecular Neuropsychiatry Research Branch, NIDA Intramural Research Program, Baltimore, MD 21224, United States. FAU - Cadet, Jean Lud AU - Cadet JL AD - Molecular Neuropsychiatry Research Branch, NIDA Intramural Research Program, Baltimore, MD 21224, United States. Electronic address: jcadet@intra.nida.nih.gov. LA - eng GR - ZIA DA000552/ImNIH/Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural DEP - 20201124 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Central Nervous System Stimulants) RN - 44RAL3456C (Methamphetamine) SB - IM MH - Animals MH - *Central Nervous System Stimulants MH - Craving MH - Drug-Seeking Behavior MH - Female MH - Gene Expression MH - Male MH - *Methamphetamine MH - Rats MH - Self Administration PMC - PMC8175033 MID - NIHMS1705565 OTO - NOTNLM OT - Methamphetamine self-administration OT - addiction OT - hippocampus OT - prefrontal cortex OT - sexual dimorphism COIS- CONFLICT OF INTEREST The authors declare that they have no conflict of interest. EDAT- 2020/11/27 06:00 MHDA- 2021/05/15 06:00 PMCR- 2021/06/03 CRDT- 2020/11/26 20:08 PHST- 2020/08/17 00:00 [received] PHST- 2020/11/04 00:00 [revised] PHST- 2020/11/15 00:00 [accepted] PHST- 2020/11/27 06:00 [pubmed] PHST- 2021/05/15 06:00 [medline] PHST- 2020/11/26 20:08 [entrez] PHST- 2021/06/03 00:00 [pmc-release] AID - S0306-4522(20)30742-9 [pii] AID - 10.1016/j.neuroscience.2020.11.025 [doi] PST - ppublish SO - Neuroscience. 2021 Jan 1;452:265-279. doi: 10.1016/j.neuroscience.2020.11.025. Epub 2020 Nov 24.