Potentiation in phencyclidine-induced serotonin-mediated behaviors after intracerebroventricular administration of 5,7-dihydroxytryptamine in rats.
Phencyclidine (PCP)-induced behaviors were compared with 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)- and p-chloroamphetamine-induced behaviors in rats pretreated with ritanserin or 5,7-dihydroxytryptamine (5,7-DHT) in order to investigate whether PCP interacts with 5-hydroxytryptamine2 (5-HT2) receptors. Head-twitch and wet-dog shake induced by p-chloroamphetamine, a 5-HT releaser, and head-twitch induced by PCP were blocked completely by pretreatment with ritanserin, a specific 5-HT2 receptor blocker, but other behaviors induced by p-chloroamphetamine, PCP and 5-MeODMT, a 5-HT agonist, were not. The intensity of head-weaving, turning, backpedalling and hind-limb abduction induced by 5-MeODMT and the intensity of head-weaving, turning and head-twitch induced by PCP were markedly greater in the rats 2 weeks after the 5,7-DHT, a 5-HT neurotoxin-injection. Contrarily, 5-HT-mediated behaviors induced by p-chloroamphetamine were attenuated in the 5,7-DHT-treated rats. 5,7-DHT-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 rat brain, but decreased the brain level of 5-HT (41% of control). These results may indicate that PCP as a 5-HT2 agonist induces head-twitch via 5-HT2 receptors, and that PCP induces head-weaving and turning via 5-HT1 receptors and/or some other mechanisms in rats.
Nabeshima
T
T
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
Yamaguchi
K
K
Ishikawa
K
K
Furukawa
H
H
Kameyama
T
T
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001679:Biogenic Amines / Q000032:analysis; D001923:Brain Chemistry / Q000187:drug effects; D004102:Dihydroxytryptamines / Q000494:pharmacology*; D004357:Drug Synergism; D007276:Injections, Intraventricular; D008297:Male; D008732:Methoxydimethyltryptamines / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D017478:Receptors, Phencyclidine; D011985:Receptors, Serotonin / Q000032:analysis / Q000187:drug effects*; D016713:Ritanserin; D010133:p-Chloroamphetamine / Q000494:pharmacology
D001679:Biogenic Amines; D004102:Dihydroxytryptamines; D008732:Methoxydimethyltryptamines; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D011985:Receptors, Serotonin; D016713:Ritanserin; D015116:5,7-Dihydroxytryptamine; D010133:p-Chloroamphetamine; D010622:Phencyclidine