Neuron‐specific cilia loss differentially alters locomotor responses to amphetamine in mice
| Autor: | Jeremy C. McIntyre, Thomas Everett, Kalene R. Jasso, Carlos Ramos, Patricia Pozo, Tyler W Ten Eyck, Jonté B. Roberts, Barry Setlow |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Dopamine Motor Activity Biology Nucleus accumbens Article Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Microtubule Neuroplasticity medicine Animals Cilia Amphetamine Mice Knockout Neuronal Plasticity Dopaminergic Neurons Cilium Dopaminergic respiratory system Ventral tegmental area 030104 developmental biology medicine.anatomical_structure Central Nervous System Stimulants Female Neuron Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | J Neurosci Res |
| ISSN: | 1097-4547 0360-4012 |
| DOI: | 10.1002/jnr.24755 |
| Popis: | The neural mechanisms that underlie responses to drugs of abuse are complex, and impacted by a number of neuromodulatory peptides. Within the past 10 years it has been discovered that several of the receptors for neuromodulators are enriched in the primary cilia of neurons. Primary cilia are microtubule-based organelles that project from the surface of nearly all mammalian cells, including neurons. Despite what we know about cilia, our understanding of how cilia regulate neuronal function and behavior is still limited. The primary objective of this study was to investigate the contributions of primary cilia on specific neuronal populations to behavioral responses to amphetamine. To test the consequences of cilia loss on amphetamine-induced locomotor activity we selectively ablated cilia from dopaminergic or GAD2-GABAergic neurons in mice. Cilia loss had no effect on baseline locomotion in either mouse strain. In mice lacking cilia on dopaminergic neurons, locomotor activity compared to wild- type mice was reduced in both sexes in response to acute administration of 3.0 mg/kg amphetamine. In contrast, changes in the locomotor response to amphetamine in mice lacking cilia on GAD2-GABAergic neurons were primarily driven by reductions in locomotor activity in males. Following repeated amphetamine administration (1.0 mg kg-1 day-1 over 5 days), mice lacking cilia on GAD2-GABAergic neurons exhibited enhanced sensitization of the locomotor stimulant response to the drug, whereas mice lacking cilia on dopaminergic neurons did not differ from wild-type controls. These results indicate that cilia play neuron-specific roles in both acute and neuroplastic responses to psychostimulant drugs of abuse. |
| Databáze: | OpenAIRE |
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