The effects of acute and repeated administration of ketamine on attentional performance in the five-choice serial reaction time task in rats.
Ketamine, the non-competitive antagonist of the N-methyl-d-aspartate receptors, is used in clinical and preclinical studies to produce schizophrenia-like cognitive impairments. However, the impact of ketamine on attentional functions remains poorly characterised. In the present study, we further examine the effects of ketamine on attentional processes assessed in the five-choice serial reaction time task (5-CSRTT) in rats. The applied schedules of ketamine administration have been previously demonstrated to evoke frontal-dependent set-shifting impairments. Rats were trained to reach a stable baseline performance. Afterwards, animals received a single injection of ketamine (0, 3 and 10 mg/kg, IP) 45 min before the 5-CSRTT session (experiment 1). In experiment 2, ketamine (0 and 30 mg/kg, IP) was administered after the daily test session for 10 consecutive days. The rats' performance was assessed at 22 h following ketamine administration and for 4 days after the last dose. Acute and repeated administration of ketamine disrupted rats performance on the 5-CSRTT. Reduced speed of responding and an increased number of omissions were noted in the absence of reduced food motivation. The within-session pattern of responding differed between rats treated acutely and repeatedly with ketamine. Specifically, repeated drug administration evoked an increase in omissions toward the end of the session, and this effect was not secondary to the reduced motivation. Ketamine affected performance during the withdrawal period only when testing with variable inter-trial intervals. The repeated administration of ketamine can impair rats' ability to sustain attention over the course of session, suggesting some utility for modelling attentional disturbances.
Department of Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland. Electronic address: nikifor@if-pan.krakow.pl.
Agnieszka
A
Nikiforuk
Department of Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland.
Piotr
P
Popik
D000704:Analysis of Variance; D000818:Animals; D001288:Attention / Q000187:drug effects*; D002755:Choice Behavior / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects*; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine
Animal models of schizophrenia; Attention; Five-choice serial reaction time task; Ketamine; NMDA receptor; Rats