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Peroral Exposure to Cannabis Sativa Ethanol Extract Caused Neuronal Degeneration and Astrogliosis in Wistar Rats' Prefrontal Cortex.

Olatunji Sunday Yinka, Ogunnaike Philip Olubunmi, Abijo Ayodeji Zabdiel, Owolabi Joshua Oladele, Adelodun Stephen Taiye, Adeoye Ayodele, Fasesan Oluwatoyin Adetutu, Olanrewaju John Afees, Adegbite Ademola Kayode

Annals of Neurosciences April 2023 DOI: 10.1177/09727531221120988 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Controlled animal experiment Peer reviewed
Sample size 28
Population Juvenile male Wistar rats weighing 70-100 g
Intervention Cannabis sativa
Dose 10 mg/kg, 50 mg/kg, and 100 mg/kg
Duration 21 days
Measures Open field test, Y-maze test, glutamate, acetylcholine, dopamine, Cytochrome C oxidase (CcO), Glucose 6-Phosphate Dehydrogenase (G-6-PDH), H&E, glial fibrillary acidic protein (GFAP)
Topics Cannabis
Keywords Prefrontal cortex Astrocytes Cannabis sativa Neurodegeneration
Key findings Cannabis sativa exposure raised prefrontal glutamate (100 mg/kg) and dopamine (all doses) and increased Cytochrome C oxidase and Glucose 6-Phosphate Dehydrogenase activity at 50 and 100 mg/kg. It impaired locomotor activity at 10 and 100 mg/kg and spatial memory at 100 mg/kg, and all exposed groups showed neuronal degeneration, with markedly increased GFAP astrocyte immunoreactivity at 100 mg/kg.

Abstract

Despite widespread concerns about its possible side effects, notably on the prefrontal cortex (PFC), which mediates cognitive processes, the use of Cannabis sativa 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 Cannabis sativa. To evaluate the effect of graded doses of Cannabis sativa on the PFC using behavioural, histological, and immunohistochemical approaches. Twenty-eight juvenile male Wistar rats weighing between 70 g and 100 g were procured and assigned into groups A-D (n = 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 Cannabis sativa (10 mg/kg, 50 mg/kg, and 100 mg/kg, respectively). Rats in all experimental groups were exposed to Cannabis sativa 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. Glutamate and dopamine levels were significantly increased (F = 24.44, P = .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 (F = 96.28, P = .0001) (F = 167.5, P = .0001) in groups C and D compared to the control. Cannabis sativa impaired locomotor activity and spatial memory in B and D and D, respectively. All Cannabis sativa exposed groups demonstrated evidence of neurodegeneration in the exposed groups; GFAP immunoexpression was evident in all groups with a marked increase in group D. Cannabis sativa altered neurotransmitter levels, energy metabolism, locomotor, and exploratory activity, and spatial working memory, with neuronal degeneration as well as reactive astrogliosis in the PFC.

Comparable studies

Other preclinical and animal studies on cannabis, most cited first.

Study Year Design Participants
Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors Mice 2015 Preclinical study
Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). hMDR1- and hBCRP-transfected HEK293 cells and hMDR1- and hBCRP-MDCKII cells 2010 In vitro study
Long-term hippocampal interneuronopathy drives sex-dimorphic spatial memory impairment induced by prenatal THC exposure Mice prenatally exposed to THC, including conditional CB1R knockout mice 2020 Animal experimental study
Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway Mice exposed to chronic THC early in life 2018 Animal experimental study
Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain Spontaneously hypertensive rats (SHRs) and Wistar rats 2014 Animal experimental study

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