Behavioral effects of psychostimulants in mutant mice with cell-type specific deletion of CB2 cannabinoid receptors in dopamine neurons
| Autor: | Qing-Rong Liu, Branden Sanabria, Zhicheng Lin, Juan Zhao, Emmanuel S. Onaivi, Norman Schanz, Ana Canseco-Alba |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Nicotine
endocrine system medicine.medical_specialty Time Factors Cannabinoid receptor Tyrosine 3-Monooxygenase Eukaryotic Initiation Factor-3 Mice Transgenic Hyperkinesis Article Statistics Nonparametric Receptor Cannabinoid CB2 Mice 03 medical and health sciences Behavioral Neuroscience 0302 clinical medicine Cocaine Dopamine Internal medicine medicine Animals RNA Messenger Amphetamine 030304 developmental biology Dopamine transporter Dopamine Plasma Membrane Transport Proteins 0303 health sciences Tyrosine hydroxylase biology Cannabinoids Chemistry Dopaminergic Neurons Methamphetamine Conditioned place preference Mice Inbred C57BL Endocrinology medicine.anatomical_structure Gene Expression Regulation nervous system Dopaminergic pathways biology.protein Conditioning Operant Central Nervous System Stimulants Locomotion 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Behavioural Brain Research. 360:286-297 |
| ISSN: | 0166-4328 |
| DOI: | 10.1016/j.bbr.2018.11.043 |
| Popis: | Activation of the endocannabinoid system modulate dopaminergic pathways that are involved in the effects of psychostimulants including amphetamine , cocaine, nicotine and other drugs of abuse. Genetic deletion or pharmacological activation of CB2 cannabinoid receptor is involved in the modulation of the effects of psychostimulants and their rewarding properties. Here we report on the behavioral effects of psychostimulants in DAT- Cnr2 conditional knockout (cKO) mice with selective deletion of type 2 cannabinoid receptors in dopamine neurons. There was enhanced psychostimulant induced hyperactivity in DAT- Cnr2 cKO mice, but the psychostimulant-induced sensitization was absent in DAT-Cnr2 cKO compared to the WT mice. Intriguingly, lower doses of amphetamine reduced locomotor activity of the DAT-Cnr 2 cKO mice. While cocaine, amphetamine and methamphetamine produced robust conditioned place preference (CPP) in both DAT- Cnr2 cKO and WT mice, nicotine at the dose used induced CPP only in the WT but not in the DAT-Cn2 cKO mice. However, pre-treatment with the CB2R selective agonist JWH133, blocked cocaine and nicotine induced CPP in the WT mice. The deletion of CB2Rs in dopamine neurons modified the levels of tyrosine hydroxylase , and reduced the expression of dopamine transporter gene expression in DAT- Cnr2 cKO midbrain region. Taken together, our data suggest that CB2Rs play a role in the modulation of dopamine-related effects of psychostimulants and could be exploited as therapeutic target in psychostimulant addiction and other psychiatric disorders associated with dopamine dysregulation. |
| Databáze: | OpenAIRE |
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