Heteromer formation between cannabinoid type 1 and dopamine type 2 receptors is altered by combination cannabinoid and antipsychotic treatments
| Autor: | Melanie E. M. Kelly, Amina M. Bagher, James T. Toguri, Alexander P. Young, Eileen M. Denovan-Wright, Robert B. Laprairie |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Cannabinoid receptor medicine.drug_class medicine.medical_treatment Heteromer Atypical antipsychotic Pharmacology Medium spiny neuron Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Receptor Cannabinoid CB1 medicine Haloperidol Animals Humans Cell Line Transformed Cannabinoid Receptor Agonists Cannabinoids Receptors Dopamine D2 Chemistry musculoskeletal neural and ocular physiology Typical antipsychotic Mice Inbred C57BL HEK293 Cells 030104 developmental biology Globus pallidus nervous system Drug Therapy Combination lipids (amino acids peptides and proteins) Cannabinoid 030217 neurology & neurosurgery Antipsychotic Agents medicine.drug |
| Zdroj: | Journal of Neuroscience Research. 98:2496-2509 |
| ISSN: | 1097-4547 0360-4012 |
| DOI: | 10.1002/jnr.24716 |
| Popis: | The cannabinoid type 1 (CB1 ) receptor and the dopamine type 2 (D2 ) receptor are co-localized on medium spiny neuron terminals in the globus pallidus where they modulate neural circuits involved in voluntary movement. Physical interactions between the two receptors have been shown to alter receptor signaling in cell culture. The objectives of the current study were to identify the presence of CB1 /D2 heteromers in the globus pallidus of C57BL/6J male mice, define how CB1 /D2 heteromer levels are altered following treatment with cannabinoids and/or antipsychotics, and determine if fluctuating levels of CB1 /D2 heteromers have functional consequences. Using in situ proximity ligation assays, we observed CB1 /D2 heteromers in the globus pallidus of C57BL/6J mice. The abundance of the heteromers increased following treatment with the nonselective cannabinoid receptor agonist, CP55,940. In contrast, treatment with the typical antipsychotic haloperidol reduced the number of CB1 /D2 heteromers, whereas the atypical antipsychotic olanzapine treatment had no effect. Co-treatment with CP55,940 and haloperidol had similar effects to haloperidol alone, whereas co-treatment with CP55,940 and olanzapine had similar effects to CP55,940. The observed changes were found to have functional consequences as the differential effects of haloperidol and olanzapine also applied to γ-aminobutyric acid release in STHdhQ7/Q7 cells and motor function in C57BL/6J male mice. This work highlights the clinical relevance of co-exposure to cannabinoids and different antipsychotics over acute and prolonged time periods. |
| Databáze: | OpenAIRE |
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