Effect of subchronic caffeine treatment on MK-801-induced changes in locomotion, cognition and ataxia in mice
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Published on: February 26, 2012
R V de Oliveira1, O P Dall'Igna, A B L Tort
1Departamento de Bioquímica, ICBS, UFRGS, Porto Alegre, Brazil.
Abstract:
N-Methyl-D-aspartate (NMDA) receptor antagonists cause hyperlocomotion and cognitive deficits in rodents, and caffeine-tolerant mice show diminished locomotor response to NMDA receptor antagonists. The aim of this study was to evaluate the effect of subchronic caffeine treatment on MK-801-induced hyperlocomotion, ataxia and cognitive deficits, as well as amphetamine-induced hyperlocomotion in mice. Mice were treated subchronically with caffeine (0, 0.1, 0.3 and 1 mg/ml and 1, 3 and 7 days) and evaluated for locomotor activity, working memory (delayed alternation test), long-term memory (inhibitory avoidance task) and ataxia. Hyperlocomotion induced by MK-801 (0.25 mg/kg i.p.) was diminished after 3 days and almost abolished after 7 days of caffeine treatment at the 1 mg/ml dose, and this effect was also dose-dependent. Ataxia induced by 0.5 mg/kg MK-801 was not affected by caffeine treatment, but a short-lived hyperlocomotor effect was observed. Performance deficit in the inhibitory avoidance task induced by MK-801 (0.01 mg/kg) was prevented in mice treated with caffeine for 7 days at 1 mg/ml, and perseverative errors in the T-maze by MK-801 (0.4 mg/kg) were attenuated. The locomotor effect of amphetamine (5 mg/kg) was unaffected by subchronic caffeine treatment. The findings that hyperlocomotion and cognitive effects induced by MK-801 can be specifically influenced by reduced adenosinergic activity agree with a model of adenosine hypofunction in schizophrenia, since NMDA receptor antagonists are pharmacological models for this disorder.
Insights
Subchronic caffeine treatment reduced N-Methyl-D-aspartate (NMDA) receptor antagonist-induced hyperlocomotion and cognitive deficits in mice. Caffeine specifically modulated NMDA effects without impacting amphetamine responses.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- N-Methyl-D-aspartate (NMDA) receptor antagonists induce hyperlocomotion and cognitive deficits in rodents.
- Caffeine tolerance is associated with a reduced locomotor response to NMDA receptor antagonists.
- NMDA receptor antagonists serve as pharmacological models for schizophrenia, suggesting a potential role for adenosine hypofunction.
Purpose of the Study:
- To investigate the impact of subchronic caffeine administration on MK-801-induced hyperlocomotion, ataxia, and cognitive impairments.
- To assess the effect of caffeine on amphetamine-induced hyperlocomotion.
- To explore the relationship between adenosinergic activity and NMDA receptor antagonist effects in the context of schizophrenia models.
Main Methods:
- Mice received subchronic caffeine treatment at various doses and durations.
- Locomotor activity, working memory (delayed alternation test), long-term memory (inhibitory avoidance task), and ataxia were evaluated.
- MK-801 and amphetamine were used to induce specific behavioral responses.
Main Results:
- Caffeine treatment significantly diminished MK-801-induced hyperlocomotion in a dose- and time-dependent manner.
- MK-801-induced ataxia was not affected by caffeine, though a transient hyperlocomotor effect was noted.
- Caffeine prevented MK-801-induced deficits in long-term memory and attenuated perseverative errors in the T-maze.
- Amphetamine-induced hyperlocomotion remained unaffected by subchronic caffeine treatment.
Conclusions:
- Subchronic caffeine administration selectively modulates NMDA receptor antagonist-induced behaviors, including hyperlocomotion and cognitive deficits.
- The findings support a model of adenosine hypofunction in schizophrenia, given the influence of caffeine (adenosine receptor antagonist) on NMDA receptor antagonist effects.
- Caffeine's ability to ameliorate MK-801-induced deficits suggests potential therapeutic implications for conditions involving NMDA receptor dysfunction.
