The non-selective adenosine antagonist theophylline reverses the effects of dopamine antagonism on tremor, motor activity and effort-based decision-making
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Other documents of the author: Pardo, Marta; Paul, Nicholas E.; Collins-Praino, Lyndsey; Salamone, John; Correa, Merce
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comunitat-uji-handle2:10234/8033
comunitat-uji-handle3:10234/8636
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https://doi.org/10.1016/j.pbb.2020.173035 |
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Title
The non-selective adenosine antagonist theophylline reverses the effects of dopamine antagonism on tremor, motor activity and effort-based decision-makingDate
2020Publisher
ElsevierISSN
0091-3057Bibliographic citation
PARDO, Marta, et al. The non-selective adenosine antagonist theophylline reverses the effects of dopamine antagonism on tremor, motor activity and effort-based decision-making. Pharmacology Biochemistry and Behavior, 2020, vol. 198, p. 173035.Type
info:eu-repo/semantics/articlePublisher version
https://www.sciencedirect.com/science/article/pii/S0091305720303683Version
info:eu-repo/semantics/publishedVersionSubject
Abstract
Considerable evidence indicates that adenosine and dopamine systems interact in the regulation of basal ganglia function. Nonselective adenosine antagonists such as the methylxanthine caffeine as well as selective ... [+]
Considerable evidence indicates that adenosine and dopamine systems interact in the regulation of basal ganglia function. Nonselective adenosine antagonists such as the methylxanthine caffeine as well as selective adenosine A2A antagonists have been shown to produce antiparkinsonian and antidepressant effects in animal models. The present studies were conducted to assess if another methylxantine, theophylline, can reverse motor and motivational impairments induced by dopamine antagonism in rats.
Results
Theophylline (3.75–30.0 mg/kg, IP) reversed tremulous jaw movements (TJMs), catalepsy, and locomotor suppression induced by the dopamine D2 antagonist pimozide. It also reversed TJMs induced by the muscarinic receptor agonist pilocarpine, which is a well-known tremorogenic agent. Parallel studies assessed the ability of theophylline (5.0–20.0 mg/kg, IP) to reverse the changes in effort-related choice behavior induced by the dopamine D1 antagonist ecopipam (0.2 mg/kg, IP) and the D2 antagonist haloperidol (0.1 mg/kg, IP). Rats were tested on two different operant choice tasks which assess the tendency to work for a preferred reinforcer by lever pressing (for palatable pellets or a high 5% sucrose solution) vs. approaching and consuming a less preferred reinforcer (freely available lab chow or a less concentrated 0.3% sucrose solution). Theophylline restored food and sucrose-reinforced lever pressing in animals treated with the D2 antagonist. However, it was unable to reverse the effects of the D1 antagonist. Overall, the effects of theophylline resembled those previously reported for adenosine A2A antagonists, and suggest that theophylline could be clinically useful for the treatment of motor and motivational symptoms in humans. [-]
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Pharmacology Biochemistry and Behavior, Volume 198, 2020.Investigation project
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