Cilia loss on distinct neuron populations differentially alters cocaine-induced locomotion and reward.

Autor:	Everett T; Department of Neuroscience, University of Florida, Gainesville, FL, USA., Ten Eyck TW; Department of Neuroscience, University of Florida, Gainesville, FL, USA., Wu CH; Department of Neuroscience, University of Florida, Gainesville, FL, USA., Shelowitz AL; Department of Neuroscience, University of Florida, Gainesville, FL, USA., Stansbury SM; Department of Neuroscience, University of Florida, Gainesville, FL, USA., Firek A; Department of Neuroscience, University of Florida, Gainesville, FL, USA., Setlow B; Department of Psychiatry, University of Florida, Gainesville, FL, USA.; Center for Addiction Research and Education, University of Florida, Gainesville, FL, USA., McIntyre JC; Department of Neuroscience, University of Florida, Gainesville, FL, USA.; Center for Addiction Research and Education, University of Florida, Gainesville, FL, USA.
Jazyk:	angličtina
Zdroj:	Journal of psychopharmacology (Oxford, England) [J Psychopharmacol] 2024 Feb; Vol. 38 (2), pp. 200-212. Date of Electronic Publication: 2023 Dec 27.
DOI:	10.1177/02698811231219058
Abstrakt:	Background: Neuronal primary cilia are being recognized for their role in mediating signaling associated with a variety of neurobehaviors, including responses to drugs of abuse. They function as signaling hubs, enriched with a diverse array of G-protein coupled receptors (GPCRs), including several associated with motivation and drug-related behaviors. However, our understanding of how cilia regulate neuronal function and behavior is still limited. Aims: The objective of the current study was to investigate the contributions of primary cilia on specific neuronal populations to behavioral responses to cocaine. Methods: To test the consequences of cilia loss on cocaine-induced locomotion and reward-related behavior, we selectively ablated cilia from dopaminergic or GAD2-GABAergic neurons in mice. Results: Cilia ablation on either population of neurons failed to significantly alter acute locomotor responses to cocaine at a range of doses. With repeated administration, mice lacking cilia on GAD2-GABAergic neurons showed no difference in locomotor sensitization to cocaine compared to wild-type (WT) littermates, whereas mice lacking cilia on dopaminergic neurons exhibited reduced locomotor sensitization to cocaine at 10 and 30 mg/kg. Mice lacking cilia on GAD2-GABAergic neurons showed no difference in cocaine conditioned place preference (CPP), whereas mice lacking cilia on dopaminergic neurons exhibited reduced CPP compared to WT littermates. Conclusions: Combined with previous findings using amphetamine, our results show that behavioral effects of cilia ablation are cell- and drug type-specific, and that neuronal cilia contribute to modulation of both the locomotor-inducing and rewarding properties of cocaine. Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Databáze:	MEDLINE
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