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The Effects of Chronic Marijuana Administration on 6-OHDA-Induced Learning & Memory Impairment and Hippocampal Dopamine and Cannabinoid Receptors Interaction in Male Rats

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Abstract

There are general inhibitory effects of exo-cannabinoids on dopamine-mediated behaviors. Many studies suggested the interaction between cannabinoid receptors and dopamine receptors in the brain that affect cognition behaviors. In this paper, we investigate the effects of marijuana on 6-OHDA-induced cognitive impairments and the expression of dopamine and cannabinoid receptors in the hippocampus of male rats. 42 rats were divided into six groups. 6-hydroxy dopamine (6-OHDA) was administrated into the substantia nigra. Marijuana (60 mg/kg; i.p.) was administered 28 days, one week after the 6-OHDA injection. Morris water maze (MWM) and novel object recognition tests were performed. The hippocampal expression levels of cannabinoid receptors and D1 and D2 dopamine receptors evaluate by real-time PCR. The results showed marijuana improved the spatial learning and memory disorders caused by 6-OHDA in the MVM task and novel object recognition test. Additionally, the level of both D1 and D2 mRNA was decreased in 6-OHDA-treated animals and marijuana consumption only increased the hippocampal level of D1 mRNA. Moreover, the level of hippocampal CB1 mRNA in 6-OHDA- treated rats was higher than in control rats. However, the hippocampal level of CB2 mRNA was decreased in 6-OHDA- treated rats. Marijuana consumption caused a significant decrease in CB1 mRNA level and an increase in CB2 mRNA level in 6-OHDA + marijuana group. Therefore, marijuana may be helpful for learning & memory disorders, D1, and D2 dopamine receptors, and cannabinoid receptor alteration in patients with Parkinson’s disease.

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Data Availability

The data that support the findings of this study are available on request from the corresponding author.

Abbreviations

PD:

Parkinson’s disease

6-OHDA:

6-hydroxy dopamine

SNc:

substantia nigra pars compacta

D1R:

dopamine D1 receptors

D1R:

dopamine D1 receptors

CB1:

cannabinoid receptor1

CB2:

cannabinoid receptor2

THC:

Δ9-tetrahydrocannabinol

DA:

dopamine

MWM:

Morris Water Maze

NOR:

novel object recognition

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Funding

This work was supported by the Kerman Neuroscience Research Center (Grant No.97 − 46/KNRC) and Zahedan University of Medical Sciences (Grant No. 9178).

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Authors and Affiliations

  1. Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran

    Elham Haghparast

  2. Kerman Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

    Elham Haghparast & Vahid Sheibani

  3. Department of Physiology, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

    Gholamreza Komeili

  4. Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Disease, Zahedan University of Medical Sciences, Zahedan, Iran

    Mohadeseh Chahkandi

  5. Infection Diseases and Tropical Medicine Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Disease, Zahedan University of Medical Sciences, Zahedan, Iran

    Nahid Sepehri Rad

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  1. Elham Haghparast
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Contributions

Elham Haghparast: Project administration, Formal analysis, Software, Investigation, Writing - Original Draft, Writing- Review & Editing. Vahid Sheibani: Conceptualization, Supervision, Methodology. Gholamrza Komaili: Conceptualization, Supervision, Methodology. Mohadeseh Chahkandi: Project administration, Writing - Original Draft. Nahid Sepehri Rad: Project administration.

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Correspondence to Elham Haghparast.

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The authors declare that they have no competing interests.

Ethics Approval

All experimental protocols and treatments were approved by the Ethics Committee of Kerman Neuroscience Research Center (Ethics Code: EC/97 − 46/KNRC) and Zahedan University of Medical Science (Ethics Code: IR.ZAUMS.REC.1398.138).

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Haghparast, E., Sheibani, V., Komeili, G. et al. The Effects of Chronic Marijuana Administration on 6-OHDA-Induced Learning & Memory Impairment and Hippocampal Dopamine and Cannabinoid Receptors Interaction in Male Rats. Neurochem Res 48, 2220–2229 (2023). https://doi.org/10.1007/s11064-023-03899-8

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