Abstract
Phencyclidine (PCP) is known to be an inhibitor of serotonin (5-HT) uptake and to increase serotonergic activity. The development of tolerance to serotonergic stereotyped behaviors induced by repeated PCP treatment and changes of 5-HT transporters were examined. Backpedalling was significantly reduced in frequency following 14 days PCP treatment (7.5 mg/kg per day). Furthermore, repeated PCP treatment decreased the equilibrium dissociation constant ( K d) of [ 3H]paroxetine binding to 5-HT transporters in whole brain excluding the cerebellum without any change of maximum number of binding sites ( B max). Single treatment with PCP failed to change binding parameters. These results indicate that repeated PCP treatment causes tolerance in serotonergic stereotyped behavior and increases affinity of 5-HT transporters for [ 3H]paroxetine binding. The increased affinity of 5-HT transporters could represent compensatory responses to chronic inhibition of 5-HT uptake by PCP.
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