Background: Despite widespread concerns about its possible side effects, notably on the prefrontal cortex (PFC), which mediates cognitive processes, the use of as a medicinal and recreational drug is expanding exponentially. This study evaluated possible behavioral alterations, neurotransmitter levels, histological, and immunohistochemical changes in the PFC of Wistar rats exposed to .

Purpose: To evaluate the effect of graded doses of on the PFC using behavioural, histological, and immunohistochemical approaches.

Methods: Twenty-eight juvenile male Wistar rats weighing between 70 g and 100 g were procured and assigned into groups A-D ( = 7 each). Group A served as control which received distilled water only as a placebo; rats in groups B, C, and D which were the treatment groups were orally exposed to graded doses of (10 mg/kg, 50 mg/kg, and 100 mg/kg, respectively). Rats in all experimental groups were exposed to for 21 days, followed by behavioral tests using the open field test for locomotor, anxiety, and exploratory activities, while the Y-maze test was for spatial memory assessment. Rats for biochemical analysis were cervically dislocated and rats for tissue processing were intracardially perfused following neurobehavioral tests. Sequel to sacrifice, brain tissues were excised and prefrontal cortices were obtained for the neurotransmitter (glutamate, acetylcholine, and dopamine) and enzymatic assay (Cytochrome C oxidase (CcO) and Glucose 6- Phosphate Dehydrogenase-G-6-PDH). Brain tissues were fixed in 10% Neutral Buffered Formalin (NBF) for histological demonstration of the PFC cytoarchitecture using H&E and glial fibrillary acidic protein (GFAP) for astrocyte evaluation.

Results: Glutamate and dopamine levels were significantly increased ( = 24.44, = .0132) in groups D, and B, C, and D, respectively, compared to control; likewise, the activities of CcO and G-6-PDH were also significantly elevated ( = 96.28, = .0001) ( = 167.5, = .0001) in groups C and D compared to the control. impaired locomotor activity and spatial memory in B and D and D, respectively. All exposed groups demonstrated evidence of neurodegeneration in the exposed groups; GFAP immunoexpression was evident in all groups with a marked increase in group D.

Conclusion: altered neurotransmitter levels, energy metabolism, locomotor, and exploratory activity, and spatial working memory, with neuronal degeneration as well as reactive astrogliosis in the PFC.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10496793PMC
http://dx.doi.org/10.1177/09727531221120988DOI Listing

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