Development of tolerance and supersensitivity to phencyclidine in rats after repeated administration of phencyclidine.
European journal of pharmacology March 3, 1987 T Nabeshima, H Fukaya, K Yamaguchi et al. 70 citations
Repeated administration of phencyclidine (PCP) to rats produced opposite effects on different behaviors: tolerance developed for back-pedalling, head-weaving, and turning, while sniffing, rearing, and ambulation became more sensitive (supersensitivity). Tests with specific drugs showed that serotonin-related behaviors weakened, whereas dopamine-related behaviors strengthened. PCP increased dopamine and serotonin levels in the nucleus accumbens and the HVA-to-dopamine ratio in the striatum. No changes occurred in sleep time or brain PCP clearance, indicating no effect on liver metabolism. The findings suggest that repeated PCP use alters dopamine and serotonin systems, with increased mesolimbic dopamine function likely underlying the supersensitivity.