PMID- 32784005 OWN - NLM STAT- MEDLINE DCOM- 20211029 LR - 20211029 IS - 1873-2747 (Electronic) IS - 0361-9230 (Linking) VI - 164 DP - 2020 Nov TI - Maternal separation plus social isolation during adolescence reprogram brain dopamine and endocannabinoid systems and facilitate alcohol intake in rats. PG - 21-28 LID - S0361-9230(20)30583-9 [pii] LID - 10.1016/j.brainresbull.2020.08.002 [doi] AB - Adverse early life experiences, i.e. abusive parenting, during postnatal development, induce long-lasting effects on the stress response systems and behavior. Such changes persist throughout an individual's life, making him/her vulnerable to suffer psychiatric disorders, including anxiety disorders and drug addiction. Rat pup maternal separation (MS) is a widely used rodent early-life stress model. MS induces changes in the dopamine and endocannabinoid systems in the nucleus accumbens (NAcc) that facilitate alcohol consumption. In this study, our endeavor was to determine if social isolation during adolescence (aSI) was as efficient as MS to facilitate alcohol intake; and moreover, if their combination (MS + aSI) induces even higher alcohol intake and exacerbates anxiety-like behaviors. Also, we evaluated dopamine and endocannabinoid receptors in the NAcc to describe potential changes caused by MS, aSI or both. Wistar rats were reared under 4 different conditions: non-MS + social housing (SH), MS + SH, non-MS + aSI and MS + aSI. Once these rats became adults they were submitted to a voluntary alcohol intake protocol for 10 days. Similar groups of rats with no exposure to alcohol whatsoever, were sacrificed to dissect out the NAcc to analyze the expression of cannabinoid (CB1R and CB2R) and dopamine (D2R and D3R) receptors. Results showed that MS, aSI and MS + aSI increase both CB1R, D2R and D3R expression in the NAcc and also increase alcohol intake and anxiety. These results suggest that early life adverse experiences induce a reprogramming of the brain's dopamine and endocannabinoid systems which increases subject's vulnerability to develop anxiety, alcohol abuse and dependence. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Amancio-Belmont, Octavio AU - Amancio-Belmont O AD - Laboratorio de Canabinoides, Departamento de Fisiologia, Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Mexico. FAU - Becerril Melendez, Alline L AU - Becerril Melendez AL AD - Laboratorio de Canabinoides, Departamento de Fisiologia, Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Mexico. FAU - Ruiz-Contreras, Alejandra E AU - Ruiz-Contreras AE AD - Laboratorio de Neurogenomica Cognitiva, Departamento de Psicofisiologia, Facultad de Psicologia. Universidad Nacional Autonoma de Mexico, Mexico. FAU - Mendez-Diaz, Monica AU - Mendez-Diaz M AD - Laboratorio de Canabinoides, Departamento de Fisiologia, Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Mexico. FAU - Prospero-Garcia, Oscar AU - Prospero-Garcia O AD - Laboratorio de Canabinoides, Departamento de Fisiologia, Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Mexico. Electronic address: opg@unam.mx. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200809 PL - United States TA - Brain Res Bull JT - Brain research bulletin JID - 7605818 RN - 0 (Endocannabinoids) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Alcohol Drinking/*metabolism MH - Animals MH - Brain/*metabolism MH - Dopamine/*metabolism MH - Endocannabinoids/*metabolism MH - *Maternal Deprivation MH - Rats MH - Rats, Wistar MH - *Social Isolation MH - Stress, Psychological/metabolism OTO - NOTNLM OT - Alcohol intake OT - Anxiety OT - Dopaminergic system OT - Endocannabinoid system OT - Maternal separation OT - Social isolation EDAT- 2020/08/14 06:00 MHDA- 2021/10/30 06:00 CRDT- 2020/08/14 06:00 PHST- 2020/04/26 00:00 [received] PHST- 2020/07/18 00:00 [revised] PHST- 2020/08/02 00:00 [accepted] PHST- 2020/08/14 06:00 [pubmed] PHST- 2021/10/30 06:00 [medline] PHST- 2020/08/14 06:00 [entrez] AID - S0361-9230(20)30583-9 [pii] AID - 10.1016/j.brainresbull.2020.08.002 [doi] PST - ppublish SO - Brain Res Bull. 2020 Nov;164:21-28. doi: 10.1016/j.brainresbull.2020.08.002. Epub 2020 Aug 9.