Effect of subchronic caffeine treatment on MK-801-induced changes in locomotion, cognition and ataxia in mice.
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.
de Oliveira
R V
RV
Departamento de Bioquímica, ICBS, UFRGS, Porto Alegre, Brazil.
Dall'Igna
O P
OP
Tort
A B L
AB
Schuh
J F
JF
Neto
P F
PF
Santos Gomes
M W
MW
Souza
D O
DO
Lara
D R
DR
D000241:Adenosine / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001259:Ataxia; D002110:Caffeine / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006801:Humans; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012559:Schizophrenia / Q000503:physiopathology
D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D002110:Caffeine; D016291:Dizocilpine Maleate; D000661:Amphetamine; D000241:Adenosine