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Ketamine-induced changes in rat behaviour: A possible animal model of schizophrenia.

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Institute of Pharmacology and Toxicology, Faculty of Medicine, Otto-von-Guericke University, Leipziger Strasse 44, 39120, Magdeburg, Germany.


It was investigated whether subchronic application of 30 mg/kg ketamine (Ket) induces reliable changes in behaviour and parameters of dopaminergic, glutamatergic, and serotonergic neurotransmissions, which might be the basis of an animal model in schizophrenia research. To test this, rats were injected with 30 mg/kg ip Ket daily for five consecutive days. In response to the first Ket injection, there was a decrease in activity time representing an acute Ket effect. Following the fifth injection, there were no differences between Ket- and saline (sal)-injected control rats in activity time, which might be a tolerance reaction. The following experiments were performed 2 or 4 weeks after Ket treatment. There were no effects on anxiety in either vehicle or Ket-treated rats using either low or high illumination levels in the elevated plus-maze. In the social interaction test, both groups of rats spent comparable times in social contact. The percentage of nonaggressive behaviour was decreased in Ket-treated rats. Two weeks after completion of the treatment, there was no effect on prepulse inhibition (PPI). Four weeks after the final Ket injection, latent inhibition (LI) was disrupted. There was no difference in the animals' activity in reaction to apomorphine (Apo) administration. Ket-treated rats injected with 0.1 mg/kg MK-801 showed an enhancement in locomotor activity. Ket treatment leads to an increase in D2 receptor binding in the hippocampus and a decrease in glutamate receptor binding in the frontal cortex. The authors did not find any changes in D1 receptor binding. The density of dopamine transporters was increased in the striatum. The density of 5-HT transporters was increased in the striatum, the hippocampus, and the frontal cortex. The results suggest that subchronic treatment with subanaesthetic doses of Ket induce schizophrenia-related alterations, which might be a useful animal model in the study of this disease.

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