Cargando…
Cell-Type Specific Deletion of CB2 Cannabinoid Receptors in Dopamine Neurons Induced Hyperactivity Phenotype: Possible Relevance to Attention-Deficit Hyperactivity Disorder
DAT-Cnr2 mice are conditional knockout (cKO) animals that do not express cannabinoid CB2 receptors (CB2R), in midbrain dopamine neurons. The hyperactivity phenotype of DAT-Cnr2 cKO mice were paradoxically reduced by low dose of amphetamine. Here, we report on the locomotor activity analysis in male...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8860836/ https://www.ncbi.nlm.nih.gov/pubmed/35211038 http://dx.doi.org/10.3389/fpsyt.2021.803394 |
_version_ | 1784654761850568704 |
---|---|
author | Canseco-Alba, Ana Sanabria, Branden Hammouda, Mariam Bernadin, Rollanda Mina, Marizel Liu, Qing-Rong Onaivi, Emmanuel S. |
author_facet | Canseco-Alba, Ana Sanabria, Branden Hammouda, Mariam Bernadin, Rollanda Mina, Marizel Liu, Qing-Rong Onaivi, Emmanuel S. |
author_sort | Canseco-Alba, Ana |
collection | PubMed |
description | DAT-Cnr2 mice are conditional knockout (cKO) animals that do not express cannabinoid CB2 receptors (CB2R), in midbrain dopamine neurons. The hyperactivity phenotype of DAT-Cnr2 cKO mice were paradoxically reduced by low dose of amphetamine. Here, we report on the locomotor activity analysis in male and female adolescent (PND 30 ± 2) mice in basal conditions and in response to different doses of amphetamine, using the Open Field (OF), Elevated Plus-Maze (EPM) tests and the Novel Object Recognition (NOR) task as a putative model of attention deficit hyperactivity disorder (ADHD). Results showed that both male and female adolescent DAT-Cnr2 mice displayed significant increases in distance traveled in the OF test compared with WT mice. However, 2 mg/kg dose of amphetamine reduced the distance traveled by the DAT-Cnr2 but was increased in the WT mice. In the EPM test of anxiety-like behavioral responses, DAT-Cnr2 spent more time in the open arms of the maze than the WT mice, suggesting a reduction in anxiety-like response. DAT-Cnr2 mice showed significant increase in the number of unprotected head dips in the maze test and in the cliff avoidance reaction (CAR) test demonstrating impulsivity and risky behavior. DAT-Cnr2 mice also exhibited deficient response in the delay decision making (DDM), with impulsive choice. Both DAT-Cnr2 and WT were able to recognize the new object in the NOR task, but the exploration by the DAT-Cnr2 was less than that of the WT mice. Following the administration of 2 mg/kg of amphetamine, the similarities and differential performances of the DAT-Cnr2 and WT mice in the EPM test and NOR task was probably due to increase in attention. Microglia activation detected by Cd11b immunolabelling was enhanced in the hippocampus in DAT-Cnr2 cKO than in WT mice, implicating neuro-immune modulatory effects of CB2R. The results demonstrates that DAT-Cnr2 cKO mice with cell-type specific deletion of CB2R in midbrain dopaminergic neurons may represent a possible model for studying the neurobiological basis of ADHD. |
format | Online Article Text |
id | pubmed-8860836 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88608362022-02-23 Cell-Type Specific Deletion of CB2 Cannabinoid Receptors in Dopamine Neurons Induced Hyperactivity Phenotype: Possible Relevance to Attention-Deficit Hyperactivity Disorder Canseco-Alba, Ana Sanabria, Branden Hammouda, Mariam Bernadin, Rollanda Mina, Marizel Liu, Qing-Rong Onaivi, Emmanuel S. Front Psychiatry Psychiatry DAT-Cnr2 mice are conditional knockout (cKO) animals that do not express cannabinoid CB2 receptors (CB2R), in midbrain dopamine neurons. The hyperactivity phenotype of DAT-Cnr2 cKO mice were paradoxically reduced by low dose of amphetamine. Here, we report on the locomotor activity analysis in male and female adolescent (PND 30 ± 2) mice in basal conditions and in response to different doses of amphetamine, using the Open Field (OF), Elevated Plus-Maze (EPM) tests and the Novel Object Recognition (NOR) task as a putative model of attention deficit hyperactivity disorder (ADHD). Results showed that both male and female adolescent DAT-Cnr2 mice displayed significant increases in distance traveled in the OF test compared with WT mice. However, 2 mg/kg dose of amphetamine reduced the distance traveled by the DAT-Cnr2 but was increased in the WT mice. In the EPM test of anxiety-like behavioral responses, DAT-Cnr2 spent more time in the open arms of the maze than the WT mice, suggesting a reduction in anxiety-like response. DAT-Cnr2 mice showed significant increase in the number of unprotected head dips in the maze test and in the cliff avoidance reaction (CAR) test demonstrating impulsivity and risky behavior. DAT-Cnr2 mice also exhibited deficient response in the delay decision making (DDM), with impulsive choice. Both DAT-Cnr2 and WT were able to recognize the new object in the NOR task, but the exploration by the DAT-Cnr2 was less than that of the WT mice. Following the administration of 2 mg/kg of amphetamine, the similarities and differential performances of the DAT-Cnr2 and WT mice in the EPM test and NOR task was probably due to increase in attention. Microglia activation detected by Cd11b immunolabelling was enhanced in the hippocampus in DAT-Cnr2 cKO than in WT mice, implicating neuro-immune modulatory effects of CB2R. The results demonstrates that DAT-Cnr2 cKO mice with cell-type specific deletion of CB2R in midbrain dopaminergic neurons may represent a possible model for studying the neurobiological basis of ADHD. Frontiers Media S.A. 2022-02-08 /pmc/articles/PMC8860836/ /pubmed/35211038 http://dx.doi.org/10.3389/fpsyt.2021.803394 Text en Copyright © 2022 Canseco-Alba, Sanabria, Hammouda, Bernadin, Mina, Liu and Onaivi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Psychiatry Canseco-Alba, Ana Sanabria, Branden Hammouda, Mariam Bernadin, Rollanda Mina, Marizel Liu, Qing-Rong Onaivi, Emmanuel S. Cell-Type Specific Deletion of CB2 Cannabinoid Receptors in Dopamine Neurons Induced Hyperactivity Phenotype: Possible Relevance to Attention-Deficit Hyperactivity Disorder |
title | Cell-Type Specific Deletion of CB2 Cannabinoid Receptors in Dopamine Neurons Induced Hyperactivity Phenotype: Possible Relevance to Attention-Deficit Hyperactivity Disorder |
title_full | Cell-Type Specific Deletion of CB2 Cannabinoid Receptors in Dopamine Neurons Induced Hyperactivity Phenotype: Possible Relevance to Attention-Deficit Hyperactivity Disorder |
title_fullStr | Cell-Type Specific Deletion of CB2 Cannabinoid Receptors in Dopamine Neurons Induced Hyperactivity Phenotype: Possible Relevance to Attention-Deficit Hyperactivity Disorder |
title_full_unstemmed | Cell-Type Specific Deletion of CB2 Cannabinoid Receptors in Dopamine Neurons Induced Hyperactivity Phenotype: Possible Relevance to Attention-Deficit Hyperactivity Disorder |
title_short | Cell-Type Specific Deletion of CB2 Cannabinoid Receptors in Dopamine Neurons Induced Hyperactivity Phenotype: Possible Relevance to Attention-Deficit Hyperactivity Disorder |
title_sort | cell-type specific deletion of cb2 cannabinoid receptors in dopamine neurons induced hyperactivity phenotype: possible relevance to attention-deficit hyperactivity disorder |
topic | Psychiatry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8860836/ https://www.ncbi.nlm.nih.gov/pubmed/35211038 http://dx.doi.org/10.3389/fpsyt.2021.803394 |
work_keys_str_mv | AT cansecoalbaana celltypespecificdeletionofcb2cannabinoidreceptorsindopamineneuronsinducedhyperactivityphenotypepossiblerelevancetoattentiondeficithyperactivitydisorder AT sanabriabranden celltypespecificdeletionofcb2cannabinoidreceptorsindopamineneuronsinducedhyperactivityphenotypepossiblerelevancetoattentiondeficithyperactivitydisorder AT hammoudamariam celltypespecificdeletionofcb2cannabinoidreceptorsindopamineneuronsinducedhyperactivityphenotypepossiblerelevancetoattentiondeficithyperactivitydisorder AT bernadinrollanda celltypespecificdeletionofcb2cannabinoidreceptorsindopamineneuronsinducedhyperactivityphenotypepossiblerelevancetoattentiondeficithyperactivitydisorder AT minamarizel celltypespecificdeletionofcb2cannabinoidreceptorsindopamineneuronsinducedhyperactivityphenotypepossiblerelevancetoattentiondeficithyperactivitydisorder AT liuqingrong celltypespecificdeletionofcb2cannabinoidreceptorsindopamineneuronsinducedhyperactivityphenotypepossiblerelevancetoattentiondeficithyperactivitydisorder AT onaiviemmanuels celltypespecificdeletionofcb2cannabinoidreceptorsindopamineneuronsinducedhyperactivityphenotypepossiblerelevancetoattentiondeficithyperactivitydisorder |