Effect of subchronic caffeine treatment on MK-801-induced changes in locomotion, cognition and ataxia in mice

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.

Caffeine, Mental Health, and Psychiatric Disorders

“…Other possibilities to be further studied are that caffeine may improve negative and cognitive symptoms and motor side effects of antipsychotics, which may contribute to high intake of caffeine by some patients with schizophrenia. Interestingly, subchronic treatment with caffeine attenuates cognitive deficits induced by an NMDA receptor antagonist used to model schizophrenia in rodents [84], and chronic treatment with caffeine renders rats less susceptible to motor effects of a typical antipsychotic [85].…”

Investigation into effects of antipsychotics on ectonucleotidase and adenosine deaminase in zebrafish brain

“…Ozyurt et al (2007) reported that ADA activity was significantly increased in the prefrontal cortex of rats in an MK-801-induced experimental psychosis model. Interestingly, chronic treatment with the adenosine receptor antagonist caffeine, which induces adaptive changes to a low endogenous adenosine signal, significantly reduced the hyperlocomotor and amnesic effects of MK-801 in mice (Dall'Igna et al 2003;de Oliveira et al 2005). ADA activity is involved in the regulation of adenosine levels in the extracellular milieu and also interacts with A 1 receptors (Franco et al 1997).…”

NMDA antagonist MK801 recreates auditory electrophysiology disruption present in autism and other neurodevelopmental disorders

“…The autism specific and overlapping with schizophrenia phenotypes are elucidated at the doses used in this study (1) [7] (2) [3,8] (3) [20] (4) [23] (5) [24] (6) [3] (7) [25] (8) [14]. …”