Dal Khatri1, Genevieve Laroche1, Marion L Grant2, Victoria M Jones3, Ryan P Vetreno4, Fulton T Crews4,5, Somnath Mukhopadhyay1,3,5. 1. Neuroscience Research Program, Biomedical Biotechnology Research Institute, North Carolina Central University, Durham, North Carolina. 2. Department of Biology, North Carolina Central University, Durham, North Carolina. 3. Department of Chemistry & Biochemistry, North Carolina Central University, Durham, North Carolina. 4. Bowles Alcohol Research Center, UNC-Chapel Hill School of Medicine, Chapel Hill, North Carolina. 5. Department of Pharmacology, UNC-Chapel Hill School of Medicine, Chapel Hill, North Carolina.
Abstract
BACKGROUND: Chronic ethanol (EtOH) exposure has been found to inhibit adult hippocampal neurogenesis in multiple models of alcohol addiction. However, acute EtOH inhibition of adult neurogenesis is not well studied. Although many abused drugs have been found to inhibit adult neurogenesis, few have studied cannabinoids or cannabinoids with EtOH, although human use of both together is becoming more common. We used an acute binge alcohol drinking model in combination with select cannabinoid receptor agonists and antagonists to investigate the actions of each alone and together on hippocampal neurogenesis. METHODS: Adult male Wistar rats were treated with an acute binge dose of EtOH (5 g/kg, i.g.), cannabinoid 1 receptor (CB1R) or cannabinoid 2 receptor (CB2R) agonists, as well as selective cannabinoid (CB) antagonists, alone or combined. Hippocampal doublecortin (DCX), Ki67, and activated cleaved caspase-3 (CC3) immunohistochemistry were used to assess neurogenesis, neuroprogenitor proliferation, and cell death, respectively. RESULTS: We found that treatment with EtOH or the CB1R agonist, arachidonoyl-2'-chloroethylamide (ACEA), and the combination significantly reduced DCX-positive neurons (DCX + IR) in dentate gyrus (DG) and increased CC3. Further, using an inhibitor of endocannabinoid metabolism, for example, JZL195, we also found reduced DCX + IR neurogenesis. Treatment with 2 different CB1R antagonists (AM251 or SR141716) reversed both CB1R agonist and EtOH inhibition of adult neurogenesis. CB2R agonist HU-308 treatment did not produce any significant change in DCX + IR. Interestingly, neither EtOH nor CB1R agonist produced any alteration in cell proliferation in DG as measured by Ki67 + cell population, but CC3-positive cell numbers increased following EtOH or ACEA treatment suggesting an increase in cell death. CONCLUSIONS: Together, these findings suggest that acute CB1R cannabinoid receptor activation and binge EtOH treatment reduce neurogenesis through mechanisms involving CB1R.
BACKGROUND: Chronic ethanol (EtOH) exposure has been found to inhibit adult hippocampal neurogenesis in multiple models of alcohol addiction. However, acute EtOH inhibition of adult neurogenesis is not well studied. Although many abused drugs have been found to inhibit adult neurogenesis, few have studied cannabinoids or cannabinoids with EtOH, although human use of both together is becoming more common. We used an acute binge alcohol drinking model in combination with select cannabinoid receptor agonists and antagonists to investigate the actions of each alone and together on hippocampal neurogenesis. METHODS: Adult male Wistar rats were treated with an acute binge dose of EtOH (5 g/kg, i.g.), cannabinoid 1 receptor (CB1R) or cannabinoid 2 receptor (CB2R) agonists, as well as selective cannabinoid (CB) antagonists, alone or combined. Hippocampal doublecortin (DCX), Ki67, and activated cleaved caspase-3 (CC3) immunohistochemistry were used to assess neurogenesis, neuroprogenitor proliferation, and cell death, respectively. RESULTS: We found that treatment with EtOH or the CB1R agonist, arachidonoyl-2'-chloroethylamide (ACEA), and the combination significantly reduced DCX-positive neurons (DCX + IR) in dentate gyrus (DG) and increased CC3. Further, using an inhibitor of endocannabinoid metabolism, for example, JZL195, we also found reduced DCX + IR neurogenesis. Treatment with 2 different CB1R antagonists (AM251 or SR141716) reversed both CB1R agonist and EtOH inhibition of adult neurogenesis. CB2R agonist HU-308 treatment did not produce any significant change in DCX + IR. Interestingly, neither EtOH nor CB1R agonist produced any alteration in cell proliferation in DG as measured by Ki67 + cell population, but CC3-positive cell numbers increased following EtOH or ACEA treatment suggesting an increase in cell death. CONCLUSIONS: Together, these findings suggest that acute CB1Rcannabinoid receptor activation and binge EtOH treatment reduce neurogenesis through mechanisms involving CB1R.
Authors: Ja Wook Koo; Scott J Russo; Deveroux Ferguson; Eric J Nestler; Ronald S Duman Journal: Proc Natl Acad Sci U S A Date: 2010-01-26 Impact factor: 11.205
Authors: Kunlin Jin; Lin Xie; Sun Hee Kim; Sophie Parmentier-Batteur; Yunjuan Sun; Xiao Ou Mao; Jocelyn Childs; David A Greenberg Journal: Mol Pharmacol Date: 2004-08 Impact factor: 4.436
Authors: K Yaragudri Vinod; Ratnakumar Yalamanchili; Panayotis K Thanos; Csaba Vadasz; Thomas B Cooper; Nora D Volkow; Basalingappa L Hungund Journal: Synapse Date: 2008-08 Impact factor: 2.562
Authors: Claudia Compagnucci; Sara Di Siena; Maria Blaire Bustamante; Daniele Di Giacomo; Monia Di Tommaso; Mauro Maccarrone; Paola Grimaldi; Claudio Sette Journal: PLoS One Date: 2013-01-23 Impact factor: 3.240
Authors: Mi Ran Choi; Jasmin Sanghyun Han; Yeung-Bae Jin; Sang-Rae Lee; In Young Choi; Heejin Lee; Hyun Cho; Dai-Jin Kim Journal: Biol Sex Differ Date: 2020-11-23 Impact factor: 5.027