Cilia loss on distinct neuron populations differentially alters cocaine-induced locomotion and reward
Thomas Everett, Tyler W Ten Eyck, Chang-Hung Wu, Amanda L Shelowitz, Sofia M Stansbury, Alexandra Firek, Barry Setlow, Jeremy C McIntyre- Pharmacology (medical)
- Psychiatry and Mental health
- Pharmacology
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.