Potentiation in phencyclidine-induced serotonin-mediated behaviors after intracerebroventricular administration of 5,7-dihydroxytryptamine in rats.
Toshitaka Nabeshima, K Yamaguchi, K Ishikawa, H Furukawa, T Kameyama
Journal of Pharmacology and Experimental Therapeutics December 1, 1987 DOI: 10.1016/s0022-3565(25)39280-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Rats (including inbred strains), pretreated with ritanserin or 5,7-dihydroxytryptamine |
| Interventions | Phencyclidine (PCP) 5-methoxy-N N-dimethyltryptamine (5-MeODMT) p-chloroamphetamine ritanserin 5 7-dihydroxytryptamine (5 7-DHT) |
| Duration | Behaviors assessed 2 weeks after 5,7-DHT injection |
| Measures | head-twitch, wet-dog shake, head-weaving, turning, backpedalling, hind-limb abduction, [3H]-5-HT binding, [3H]ketanserin binding, [3H]PCP binding, brain 5-HT level |
| Topics | Serotonin |
| Keywords | Animals Rats, inbred strains Biogenic amines Methoxydimethyltryptamines P-chloroamphetamine Piperidines Ritanserin Dihydroxytryptamines 5,7-dihydroxytryptamine Receptors, serotonin Receptors, neurotransmitter Receptors, n-methyl-d-aspartate Receptors, phencyclidine Injections, intraventricular Behavior, animal Brain chemistry Drug synergism Male |
| Key findings | Ritanserin completely blocked PCP-induced head-twitch, and 5,7-DHT lesions markedly increased PCP- and 5-MeODMT-induced head-weaving, turning, and head-twitch while attenuating p-chloroamphetamine-induced behaviors. The authors propose that PCP induces head-twitch via 5-HT2 receptors and head-weaving and turning via 5-HT1 receptors and/or other mechanisms. |
Abstract
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.
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