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Published on: October 4, 2021
Biphasic effects of oxotremorine-M on turning behavior induced by caffeine in 6-OHDA-lesioned rats
Juan Francisco Núñez-Taltavull1, Gemma Prat, Antonia Rubio
1Laboratori de Neuropsicofarmacologia, Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Departaments de Psiquiatria i de Farmacología, Universitat Autónoma de Barcelona, Barcelona, Spain.
Abstract:
This work studied the interactions between cholinergic and adenosine systems in the denervated striatum. For that purpose, we evaluated the effects of an intrastriatal administration of the muscarincic receptor agonist, oxotremorine-M on turning behavior induced by systemic caffeine in unilaterally 6-hydroxydopamine-lesioned rats. Low doses of oxotremorine-M (0.1 ng/microl) enhanced, whereas high doses (100 ng/microl) attenuated contralateral turning induced by caffeine. These results support a functional link between muscarinic and adenosinergic systems in the denervated striatum and suggest opposite actions of muscarinic M2 and M1 receptors on caffeine-induced turning behavior.
Insights
This study investigated how cholinergic and adenosine systems interact in the denervated striatum. Low doses of oxotremorine-M enhanced caffeine-induced turning, while high doses attenuated it, suggesting complex receptor actions.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- The denervated striatum exhibits altered neurotransmitter system interactions.
- Cholinergic and adenosinergic systems play crucial roles in motor control and striatal function.
Purpose of the Study:
- To investigate the functional interplay between the cholinergic and adenosine systems in the context of a denervated striatum.
- To evaluate the impact of muscarinic receptor agonism on caffeine-induced turning behavior in a rat model of Parkinson's disease.
Main Methods:
- Unilaterally 6-hydroxydopamine-lesioned rats were used to model denervation.
- Intrastriatal administration of oxotremorine-M (a muscarinic receptor agonist) was performed.
- Caffeine-induced contralateral turning behavior was measured.
Main Results:
- Low-dose oxotremorine-M (0.1 ng/microl) potentiated caffeine-induced contralateral turning.
- High-dose oxotremorine-M (100 ng/microl) attenuated caffeine-induced contralateral turning.
- Dose-dependent effects indicate complex receptor modulation.
Conclusions:
- A functional link exists between muscarinic and adenosinergic systems in the denervated striatum.
- Muscarinic M1 and M2 receptors exhibit opposing effects on caffeine-induced turning behavior.
- These findings provide insights into potential therapeutic strategies targeting these systems.

