Chronic Cannabis Extract Modulates Anxiety Behavior in Wistar Rats: VTA Histology and Catecholamine Analysis

Abstract

Cannabis, derived from the Cannabis sativa plant, has seen a surge in global use, particularly in medicinal and recreational contexts, over the past decade. The VTA, a critical component of the brain’s reward system, plays a pivotal role in motivation and addiction through its dopaminergic pathways. While research has examined the behavioral and neurochemical effects of cannabis, there is limited exploration of cannabis-induced histological changes in the VTA, thus, this study investigated the effects of chronic cannabis ethanol extract exposure on anxiety behavior, ventral tegmental area (VTA) histology, and catecholamine levels in Wistar rats. Using the Elevated Plus Maze (EPM) test, anxiety behavior was assessed across four groups exposed to varying doses (0, 50, 100, and 150 mg/kg) of cannabis extract. Histological analysis of the VTA and catecholamine quantification were conducted to evaluate structural and biochemical changes. Behavioral results indicated dose-dependent increases in anxiety, with Group 3 (100 mg/kg) showing the highest anxiety-related behaviors, evidenced by reduced open-arm exploration and increased closed-arm preference (p < 0.05). Histological analysis revealed fatty changes and inflammatory cell infiltration in the VTA, with severity increasing at higher doses. Catecholamine levels declined dose-dependent (p < 0.05), suggesting suppressed neurotransmitter synthesis or metabolism. These findings align with previous reports of cannabis-induced neurotoxicity and its biphasic effects on anxiety, extending understanding of its behavioral, structural, and biochemical impacts. The results highlight the potential risks of chronic cannabis use, particularly at higher doses, on anxiety regulation and neural integrity in the VTA.