Potentiation of phencyclidine- and serotonin agonist-induced behaviors after administration of p-chloroamphetamine in rats

Phencyclidine (PCP)-induced behaviors were compared with 5-methoxy-N,Ndimethyltryptamine (5-MeODMT)- and p-chloroamphetamine-induced behaviors in rats pretreated with ritanserin, pindolol, or p-chloroamphetamine in order to investigate whether PCP interacts with 5-hydroxytryptamine₁ (5-HT₁) and 5-HT₂ receptors. The intensity of head-weaving, forepaw treading and hind-limb abduction induced by 5-MeODMT, a 5-HT agonist, and of head-weaving induced by p-chloroamphetamine, a 5-HT releaser, or PCP were decreased by pretreatment with pindolol, a 5-HT₁ receptor blocker. Head-twitch and wet-dog shake induced by p-chloroamphetamine and head-twitch induced by PCP were completely blocked by pretreatment with ritanserin, a selective 5-HT₂ receptor blocker. The intensity of head-weaving, turning, forepaw treading, hind-limb abduction and Straub tail induced by 5-MeODMT and the intensity of head-twitch, turning and backpedalling induced by PCP were markedly increased in the rats 13 days after treatment with a high dose of p-chloroamphetamine. In addition, the intensity of 5-HT-mediated behaviors induced by 5-MeODMT and PCP in the p-chloroamphetamine-pretreated rats decreased after pretreatment with pindolol or ritanserin. By contrast, 5-HT-mediated behaviors induced by p-chloroamphetamine were attenuated in the p-chloroamphetamine-pretreated rats. p-Chloroamphetamine treatment increased the number of 5-HT₁ ([³H]5-HT), 5-HT₂ ([³H]ketanserin) and PCP ([³H]PCP) binding sites in the synaptic membrane of the rat brain, but decreased the brain levels of 5-HT and its metabolite. These results indicate the PCP induces head-weaving, turning and backpedalling via 5-HT₁ receptors and/or some other mechanisms and that, as a 5-HT₂ agonist, PCP induces head-twitch via 5-HT₂ receptors in rats.