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Reduced proconvulsant activity of caffeine in rats after a series of electroconvulsive seizures
1Department of Psychiatry, SUNY Stony Brook 11794, USA.
Abstract:
A variety of neurotransmitter receptor changes occur after a course of electroconvulsive seizures (ECS) in rats, including an increased density of adenosine A1 sites. Adenosine antagonism has been related to the proconvulsant action of methylxanthines such as caffeine. We determined tonic-clonic seizure duration in rats given ECS with caffeine (0-175 mg/kg, IP) after a course of one or six daily ECS. A single day of ECS did not affect the dose-dependent proconvulsant action of caffeine. After six daily ECS, the proconvulsant action of caffeine was reduced. After nine daily ECS, an A1 antagonist (8-cyclopentyl-1,3-dipropylxanthine) and an A2A antagonist (1-allyl-3,7-dimethyl-8-p-sulfophenylxanthine) showed reduced proconvulsant activity. The results suggest that the reduced proconvulsant action of caffeine after chronic ECS depends on adenosine antagonism.
Insights
Chronic electroconvulsive seizures (ECS) in rats reduce caffeine
Area of Science:
- Neuroscience
- Pharmacology
- Neurobiology
Background:
- Electroconvulsive seizures (ECS) induce changes in neurotransmitter receptor density in rats.
- Adenosine receptor activity is linked to the proconvulsant effects of methylxanthines like caffeine.
Purpose of the Study:
- To investigate the impact of electroconvulsive seizures (ECS) on the proconvulsant action of caffeine.
- To determine the role of adenosine antagonism in the observed effects of ECS on caffeine-induced seizures.
Main Methods:
- Rats underwent single or multiple daily courses of electroconvulsive seizures (ECS).
- Tonic-clonic seizure duration was measured after administering varying doses of caffeine.
- Specific adenosine A1 and A2A antagonists were used to assess their role after nine daily ECS treatments.
Main Results:
- A single ECS treatment did not alter caffeine's dose-dependent proconvulsant effect.
- Chronic ECS (six daily treatments) significantly reduced the proconvulsant action of caffeine.
- Adenosine A1 and A2A antagonists exhibited reduced proconvulsant activity after nine daily ECS treatments.
Conclusions:
- The proconvulsant action of caffeine is diminished following chronic electroconvulsive seizures (ECS) in rats.
- This reduction is dependent on adenosine antagonism, suggesting a role for adenosine receptors in ECS-induced neuroadaptations.