Ketamine dose-dependently induces high-frequency oscillations in the nucleus accumbens in freely moving rats.
BACKGROUND
In humans, subanesthetic doses of ketamine and recovery from ketamine anesthesia are associated with psychotic-like behavior. In rodents, ketamine produces hyperactivity, stereotypies, and abnormal social interaction used to model certain features of schizophrenia. Increasing evidence has implicated aberrant activity in the nucleus accumbens (NAc) with the pathophysiology of schizophrenia.


METHODS
Here, we examined the effect of an IP injection of ketamine (10, 25, 50, and 200 mg/kg) and d-amphetamine (3 mg/kg) on local field potentials in the rodent NAc. Locomotor activity was recorded simultaneously.


RESULTS
Spontaneous high-frequency oscillations (HFO) (140-180 Hz) were present in local field potentials recorded from the NAc. Ketamine dose-dependently induced rapid and substantial increases in HFO that correlated with behavioral hyperactivity. Similarly, large increases in HFO occurred during recovery from ketamine anesthesia. In contrast, d-amphetamine, which induced locomotor activity, produced only small increases in HFO.


CONCLUSIONS
We propose that ketamine-induced abnormal increases in HFO form part of the complex neurological changes in this model of schizophrenia. Ketamine-induced increases in HFO, although sharing similar temporal dynamics to hyperactivity, may not be functionally related to increased movement.
Hunt
Mark Jeremy
MJ
Université de Nice-Sophia Antipolis, Laboratoire de Neurobiologie et Psychopathologie, Nice, France. mhunt@nencki.gov.pl
Raynaud
Beryl
B
Garcia
Rene
R
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001143:Arousal; D001522:Behavior, Animal; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006612:High-Frequency Ventilation; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine