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.
Neuroscience letters
May 19, 1987
T Nabeshima, K Ishikawa, K Yamaguchi et al.
27 citations
Phencyclidine (PCP) causes a head-twitch response in mice and rats that is completely blocked by ritanserin, a serotonin 5-HT2 receptor antagonist, indicating the involvement of 5-HT2 receptors. The same antagonism occurs for head-twitch induced by 5-MeODMT in mice. After ritanserin treatment, PCP and 5-MeODMT still produce head-weaving in mice but not in rats. In rats, 5-MeODMT does not cause head-twitch. These results suggest that PCP-induced head-twitch in rats is mediated by 5-HT2 receptors, making it a useful model for studying those receptors, while 5-MeODMT-induced head-weaving in rats involves 5-HT1 receptors.
European journal of pharmacology
January 20, 1987
T Nabeshima, K Ishikawa, K Yamaguchi et al.
27 citations
Withdrawal from chronic methysergide, a 5-HT2 receptor blocker, potentiates phencyclidine (PCP)-induced head-twitch behavior in rats, while repeated PCP treatment leads to tolerance that is blocked by methysergide. PCP-induced behaviors (head-twitch, head-weaving, turning, backpedalling) were attenuated after 12 days of daily PCP, but head-twitch increased significantly after stopping methysergide. Binding studies showed increased Bmax of 5-HT2 and PCP receptors after methysergide withdrawal, and decreased Bmax of 5-HT2 receptors after PCP tolerance, with no affinity changes. PCP displaced [3H]ketanserin at 5-HT2 but not [3H]5-HT at 5-HT1 sites, indicating PCP produces head-twitch through agonistic action at 5-HT2 receptors.
European journal of pharmacology
July 9, 1987
T Nabeshima, K Ishikawa, K Yamaguchi et al.
17 citations
Ritanserin, a drug that blocks serotonin 5-HT2 receptors, reduced head-twitch behavior in mice caused by phencyclidine (PCP) and another serotonin-like drug, but increased head-weaving behavior. The two behaviors were inversely related. Depleting serotonin with PCPA reduced head-weaving caused by PCP plus ritanserin but not head-weaving caused by the serotonin-like drug. These results suggest PCP causes head-weaving by indirectly activating a different serotonin receptor (possibly 5-HT1) after releasing serotonin, and head-twitch by directly activating 5-HT2 receptors.