Dutt_2020_Physiol.Behav_222_112935

BACKGROUND: In the previous decade, abuse of several types of prescription drugs, particularly anxiolytics, opioid analgesics, and stimulants has increased significantly worldwide. Methylphenidate (MPH) and Alprazolam (ALZ) are extensively used drugs for the treatment of attention deficit hyperactivity disorder (ADHD) and anxiety disorders, respectively. However, these drugs have a high risk of being misused or abused alone, and their combination in some peculiar cases has shown their deleterious effects. In this study, we evaluated the extent of damage both these drugs (MPH and ALZ) may cause in the brain at different dosages. METHODS: Female Wistar rats were administered with MPH (10, 20, 40mg/kg) and ALZ (5, 10, 20mg/kg) alone and in combination. Following the treatment, neurobehavioral studies were conducted, and later brain tissue was removed for studying the extent of oxidative stress and inflammation in the hippocampus and cortex region of the brain. Further histopathological parameters, along with neurotransmitter levels, were also assessed. RESULTS: Both MPH and ALZ, in combination, enhanced oxidative stress, inflammation, and neurobehavioral alterations in a dose-dependent manner. These toxic effects were associated with histopathological alterations and neurotransmitters levels CONCLUSIONS: In this study, it is found that the combination of psychostimulant (MPH) and depressant (ALZ) tends to enhance toxicity in the brain, and their long-term usage is a significant public health concern. Therefore, their co-administration should be strictly monitored by medical practitioners, and under compulsive circumstances, their use must be restricted to lower doses.