Abstract

NEUROCOGNITIVE AND BIOCHEMICAL ALTERATIONS INDUCED BY PSYCHOACTIVE SUBSTANCES (ALCOHOL AND MARIJUANA) UNDER SUB-CHRONIC STRESS CONDITIONS IN MICE

Joffa Price Paul Kwaku, Ozakieoniso James Kemelayefa*, Emmanuel Agoghene Philip

ABSTRACT

Background: Sub-chronic stress and substance abuse are major contributors to cognitive deficits and neurobiological dysfunction. This study investigated the effects of marijuana and alcohol, individually and in combination with stress, on cognitive performance and biochemical markers in mice. Aim. To determine the effects of physical stress with psychoactive substances (alcohol and marijuana) on cognitive performance and biochemical indices. Methods: Sixty four (64) male mice were randomly divided into eight groups (n = 8): Group 1 – Normal Saline (NS), Group 2 – Stressors only (SR: restraint and sleep deprivation via music), Group 3 – Marijuana (CB), Group 4 – CB + SR, Group 5 – Alcohol (AC), Group 6 – AC + SR, Group 7 – CB + AC, and Group 8 – CB + AC + SR. Stress was induced for 31 days, after which treatments were administered for 7 days. Spatial learning and memory were assessed using the Morris Water Maze (MWM). Biochemical analyses for corticosterone and oxidative stress markers \(malondialdehyde MDA, superoxide dismutase SOD) were performed following sub chronic-stress induction. Results: Mice in the CB + SR (p < 0.03), AC + SR (p < 0.01), and CB + AC + SR (p < 0.01) groups exhibited significantly prolonged escape latencies in the MWM compared to the SR group, indicating impaired spatial memory. There was also marked elevated serum corticosterone levels and increased oxidative stress markers (MDA and SOD) were observed in all stressed groups, with the significant alterations in the CB + AC + SR group (p <0.001). Conclusion: Combined exposure to sub chronic-stress and psychoactive substances, particularly alcohol and marijuana, synergistically impairs spatial memory and induces neuroendocrine and oxidative stress. These findings highlight the compounded risks of concurrent substance use and sub-chronic stress on cognitive and physiological functions.

Keywords: Marijuana; Alcohol; Psychoactive-substances; Sub-chronic; Neurocognitive; Biochemical.