Environmental enrichment as a multisystem modulator of neurotransmitter function: mechanisms, plasticity, and therapeutic implications

Environmental enrichment (EE) has emerged as a powerful non-pharmacological strategy for reshaping brain function through experience dependent plasticity. By integrating sensory, cognitive, motor, and social stimulation, EE provides a biologically relevant framework for understanding how external environments influence neurotransmitter systems that govern mood, cognition, stress adaptation, and neurodegeneration. In this review, we examined the effects of EE on major neurotransmitter pathways, including serotonergic, dopaminergic, glutamatergic, GABAergic, cholinergic, adrenergic, and histaminergic systems. We conducted a structured narrative search of PubMed, supplemented by Google Scholar reference list searching and informed by PRISMA reporting principles. The literature search covered studies published through 4 September 2026. The initial search, completed in February 2025, included 136 articles. A supplemental update screened 108 PubMed records and identified seven additional eligible primary studies, resulting in an updated evidence synthesis comprising 143 articles. Across predominantly preclinical studies, EE was consistently associated with enhanced neurogenesis, synaptic plasticity, stress resilience, and improved behavioral and cognitive outcomes, accompanied by neurotransmitter related changes across multiple brain systems. The most robust evidence supported modulation of serotonergic, dopaminergic, glutamatergic, and GABAergic pathways, whereas adrenergic and histaminergic effects were less well characterized and often indirect. Mechanistically, these effects converged on altered receptor and transporter expression, neurotrophic signaling, CREB dependent transcriptional regulation, and epigenetic remodeling. Collectively, the evidence positions EE as a multisystem regulator of neurotransmitter function with potential relevance to mood disorders, neuroinflammation, neurodegeneration, stroke, addiction, and cognitive decline. Nevertheless, the field remains limited by the predominance of animal data and by substantial heterogeneity in enrichment paradigms. Future translational and clinical studies are needed to define the most effective EE components, timing, and intensity for therapeutic application in humans.