| First Author | Godar SC | Year | 2019 |
| Journal | Neuropharmacology | Volume | 159 |
| Pages | 107513 | PubMed ID | 30716416 |
| Mgi Jnum | J:294966 | Mgi Id | MGI:6458220 |
| Doi | 10.1016/j.neuropharm.2019.01.028 | Citation | Godar SC, et al. (2019) Gene-environment interactions in antisocial behavior are mediated by early-life 5-HT2A receptor activation. Neuropharmacology 159:107513 |
| abstractText | The ontogeny of antisocial behavior (ASB) is rooted in complex gene-environment (GxE) interactions. The best-characterized of these interplays occurs between: a) low-activity alleles of the gene encoding monoamine oxidase A (MAOA), the main serotonin-degrading enzyme; and b) child maltreatment. The purpose of this study was to develop the first animal model of this GxE interaction, to help understand the neurobiological mechanisms of ASB and identify novel targets for its therapy. Maoa hypomorphic transgenic mice were exposed to an early-life stress regimen consisting of maternal separation and daily intraperitoneal saline injections and were then compared with their wild-type and non-stressed controls for ASB-related neurobehavioral phenotypes. Maoa hypomorphic mice subjected to stress from postnatal day (PND) 1 through 7 - but not during the second postnatal week - developed overt aggression, social deficits and abnormal stress responses from the fourth week onwards. On PND 8, these mice exhibited low resting heart rate - a well-established premorbid sign of ASB - and a significant and selective up-regulation of serotonin 5-HT2A receptors in the prefrontal cortex. Notably, both aggression and neonatal bradycardia were rescued by the 5-HT2 receptor antagonist ketanserin (1-3mgkg(-1), IP), as well as the selective 5-HT2A receptor blocker MDL-100,907 (volinanserin, 0.1-0.3mgkg(-1), IP) throughout the first postnatal week. These findings provide the first evidence of a molecular basis of GxE interactions in ASB and point to early-life 5-HT2A receptor activation as a key mechanism for the ontogeny of this condition. This article is part of the Special Issue entitled 'The neuropharmacology of social behavior: from bench to bedside'. |
