Spontaneous alternation behaviour in rats: kynurenic acid attenuated deficits induced by MK-801.
The present study was undertaken to investigate the effects of pharmacological modulation of the NMDA receptors on spontaneous alternation behaviour. The performance of rats treated with MK-801 and kynurenic acid (KYNA) was assessed in the cross-arm-maze. We evaluated: (a) the total number of arm entries representing locomotor activity, (b) spontaneous variation of different arms thought to reflect alternation performance. In the first experiment, MK-801 (0.01, 0.025, 0.05, 0.1 and 0.2 mg/kg, i.p.) was given 30 min prior to the testing. Beginning the dose of 0.05 mg/kg the drug increased locomotion and impaired alternation performance. An ability of animals to enter subsequently three or four different arms was reduced significantly. In the second experiment, the dose of 0.05 mg/kg was chosen as the lowest possible dose of MK-801 producing marked behavioural impairment. KYNA (0.3, 3 and 30 mg/kg, s.c.) was administered 60 min prior to the MK-801. While all KYNA doses prevented hyperlocomotion, only the highest dose (30 mg/kg) maintained alternation score at the control levels, i.e. the KYNA plus MK-801 treated animals alternated regularly three or four different arms. The results suggest different sensitivity of the two behavioural systems, i.e. locomotion and space orientation, towards pharmacological insult. In conclusion, the study confirmed protective behavioural effects of KYNA given in sufficient amounts and sufficiently long prior MK-801.
Hlinák
Zdenek
Z
Institute of Physiology, Academy of Sciences of the Czech Republic, Vídenská 1083, 142 20 Prague 4, Czech Republic. koktova@biomed.cas.cz
Krejcí
Ivan
I
D000818:Animals; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects*; D018698:Glutamic Acid / Q000502:physiology; D007736:Kynurenic Acid / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D018697:Nootropic Agents / Q000494:pharmacology; D010889:Piracetam / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D018691:Excitatory Amino Acid Antagonists; D018697:Nootropic Agents; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D007736:Kynurenic Acid; D010889:Piracetam