PMID- 26566284 OWN - NLM STAT- MEDLINE DCOM- 20160629 LR - 20191210 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 11 DP - 2015 TI - Reduced Contextual Discrimination following Alcohol Consumption or MDMA Administration in Mice. PG - e0142978 LID - 10.1371/journal.pone.0142978 [doi] LID - e0142978 AB - The recreational drugs, alcohol and 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") have both been shown to cause immune activation in vivo, and they are linked to cognitive impairment and anxiety-like behaviors in rodents. The neuronal effects of these drugs in the hippocampal area, an area that has been a focus of studies aiming to explain the mechanisms underlying anxiety related-disorders, remains poorly understood. Therefore we investigated the specific inflammatory impact of alcohol and MDMA on this area of the brain and on a hippocampal-related behavioral task. We centered our study on two inflammatory factors linked to anxiety-related disorders, namely Interleukin-1beta (IL-1beta) and brain-derived neurotrophic factor (BDNF). We subjected drug-consuming mice to a battery of behavioral tests to evaluate general activity, anxiety-like and depressive-live behaviors. We then introduced them to a contextual fear discrimination task and immune-related effects were examined by immunohistochemical and biochemical studies. Our results suggest that there is a relationship between the induction of immune activated pathways by voluntary alcohol consumption and a high-dose MDMA. Furthermore, the ability of mice to perform a contextual fear discrimination task was impaired by drug consumption and we report long term inflammatory alterations in the hippocampus even several weeks after drug intake. This information will be helpful for discovering new selective drug targets, and to develop treatments and preventive approaches for patients with anxiety-related disorders. FAU - Johansson, Emily M AU - Johansson EM AD - Neurobiology of Behaviour Research Group (GReNeC), Department of Health and Experimental Sciences, Universitat Pompeu Fabra, IMIM, Hospital del Mar Medical Research Institute, Barcelona Biomedical Research Park C/Dr. Aiguader 88, 08003, Barcelona, Spain. FAU - Garcia-Gutierrez, Maria S AU - Garcia-Gutierrez MS AD - Instituto de Neurociencias, Universidad Miguel Hernandez-CSIC, Avda. Ramon y Cajal s/n, San Juan de Alicante, Alicante, Spain. AD - Red Tematica de Investigacion Cooperativa en Salud (RETICS), Red de Trastornos Adictivos, Instituto de Salud Carlos III, Madrid, Spain. FAU - Moscoso-Castro, Maria AU - Moscoso-Castro M AD - Neurobiology of Behaviour Research Group (GReNeC), Department of Health and Experimental Sciences, Universitat Pompeu Fabra, IMIM, Hospital del Mar Medical Research Institute, Barcelona Biomedical Research Park C/Dr. Aiguader 88, 08003, Barcelona, Spain. FAU - Manzanares, Jorge AU - Manzanares J AD - Instituto de Neurociencias, Universidad Miguel Hernandez-CSIC, Avda. Ramon y Cajal s/n, San Juan de Alicante, Alicante, Spain. AD - Red Tematica de Investigacion Cooperativa en Salud (RETICS), Red de Trastornos Adictivos, Instituto de Salud Carlos III, Madrid, Spain. FAU - Valverde, Olga AU - Valverde O AD - Neurobiology of Behaviour Research Group (GReNeC), Department of Health and Experimental Sciences, Universitat Pompeu Fabra, IMIM, Hospital del Mar Medical Research Institute, Barcelona Biomedical Research Park C/Dr. Aiguader 88, 08003, Barcelona, Spain. AD - Red Tematica de Investigacion Cooperativa en Salud (RETICS), Red de Trastornos Adictivos, Instituto de Salud Carlos III, Madrid, Spain. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151113 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Hallucinogens) RN - 0 (IL1B protein, mouse) RN - 0 (Illicit Drugs) RN - 0 (Interleukin-1beta) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM MH - *Alcohol Drinking MH - Animals MH - Anxiety/drug therapy MH - Behavior, Animal/drug effects MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cognition/drug effects MH - Discrimination Learning/*drug effects MH - Fear/drug effects MH - Gene Expression Profiling MH - Gene Expression Regulation/*drug effects MH - Hallucinogens/adverse effects MH - Hippocampus/drug effects MH - Illicit Drugs/chemistry MH - Immunohistochemistry MH - Inflammation MH - Interleukin-1beta/*metabolism MH - Male MH - Maze Learning MH - Mice MH - Motor Activity/drug effects MH - N-Methyl-3,4-methylenedioxyamphetamine/*adverse effects MH - Neurons/drug effects MH - Polymerase Chain Reaction PMC - PMC4643963 COIS- Competing Interests: The authors declare no conflicts of interest. EDAT- 2015/11/14 06:00 MHDA- 2016/06/30 06:00 PMCR- 2015/11/13 CRDT- 2015/11/14 06:00 PHST- 2015/04/09 00:00 [received] PHST- 2015/10/29 00:00 [accepted] PHST- 2015/11/14 06:00 [entrez] PHST- 2015/11/14 06:00 [pubmed] PHST- 2016/06/30 06:00 [medline] PHST- 2015/11/13 00:00 [pmc-release] AID - PONE-D-15-15011 [pii] AID - 10.1371/journal.pone.0142978 [doi] PST - epublish SO - PLoS One. 2015 Nov 13;10(11):e0142978. doi: 10.1371/journal.pone.0142978. eCollection 2015.