Dysfunctional mesocortical dopamine circuit at pre-adolescence is associated to aggressive behavior in MAO-A hypomorphic mice exposed to early life stress. (15th November 2019)

• Record Type: Journal Article
• Authors: Frau, Roberto; Fanni, Silvia; Serra, Valeria; Simola, Nicola; Godar, Sean C.; Traccis, Francesco; Devoto, Paola; Bortolato, Marco; Melis, Miriam
• Is Part Of: Neuropharmacology. Volume 159(2019)
• Publication Date: 2019-11-15
• Subjects: Aggression -- Dopamine -- MAOA -- Prefrontal cortex -- Ventral tegmental area; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2019.01.032
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Aggressive behavior (AB) is a multifaceted disorder based on the interaction between genetic and environmental factors whose underlying mechanisms remain elusive. The best-characterized gene by environment (GxE) interaction for AB is the relationship between child neglect/abuse and low-activity alleles of the monoamine-oxidase A (MAOA) gene. MAOA oxidizes monoamines like serotonin and dopamine, whose aberrant signaling at discrete developmental ages plays a pivotal role in the ontogeny of AB. Here, we investigated the impact of this GxE on dopamine function at pre-adolescence by exposing hypomorphic MAOA (MAO Neo ) mice to early life stress (ES) and by performing behavioral and ex vivo electrophysiological analyses in the ventral tegmental area (VTA) and the prefrontal cortex (PFC). MAOA Neo ES mouse dopamine neurons exhibited an enhanced post-synaptic responsiveness to excitatory inputs, aberrant plasticity in the PFC, and an AB. Systemic administration of the selective antagonist at dopamine D1 receptors SCH23390 fully restored PFC function and rescued AB. Collectively, these findings reveal that dysfunctional mesocortical dopamine signaling at pre-adolescence ties to AB in the MAOA Neo ES mouse, and identify dopamine D1 receptor as a molecular target to be exploited for an age-tailored therapy. This article is part of the Special Issue entitled 'The neuropharmacology of social behavior: from bench to bedside'. Highlights: Early stress biases dopamine function and elicits aggression in MAOA Neo mice. Preadolescence is a critical developmental milestone for ontogeny of aggressiveness. DA-D1 receptor as a molecular target for early intervention in aggressive behavior.