Involvement of 5-HT2 receptors in the behaviours produced by intrathecal administration of selected 5-HT agonists and the TRH analogue (CG 3509) to rats.
1. The behavioural effects of the intrathecal injection of a thyrotrophin-releasing hormone (TRH) analogue L-orotyl-L-histidyl-prolineamide (CG 3509, 0.5 micrograms), the non-selective 5-HT1 and 5-HT2 receptor agonist 5-methoxy-N,N'-dimethyltryptamine (5-MeODMT, 2-100 micrograms) and the selective 5-HT2 receptor agonist 2,5-dimethoxy-alpha,4-dimethyl-benzene ethamine hydrochloride (DOM, 2-25 micrograms) were compared with the response of systemically administered 5-MeODMT (2 mg kg-1, i.p.) in rats, to establish whether the agonist-induced behaviours were mediated by bulbospinal 5-HT1 or 5-HT2 receptors. 2. Intrathecal injection of 5-MeODMT or DOM produced dose-related back muscle contractions (a previously undocumented behaviour) and wet-dog shakes which were both markedly attenuated by ritanserin pretreatment (1 mg kg-1, i.p.) indicating the involvement of 5-HT2 receptors. In contrast, reciprocal forepaw treading, flat body posture and Straub-tail were evoked by 5-MeODMT but not by DOM indicating that these behaviours were not produced by 5-HT2 receptor activation alone. However, as ritanserin pretreatment reduced the reciprocal forepaw treading induced by intrathecal 5-MeODMT, this behaviour may be facilitated by 5-HT2 receptor activation. 3. Intrathecal 5,7-dihydroxytryptamine (5,7-DHT, 2 x 150 micrograms) treatment decreased thoraco-lumbar spinal cord 5-HT (-95%) and potentiated the back muscle contractions produced by intrathecal DOM injection without altering the wet-dog shake behaviour. None of the components of the 5-HT syndrome produced by 5-MeODMT (2 mg kg-1, i.p.), with the exception of a small increase in wet-dog shakes, was significantly altered by intrathecal 5,7-DHT (which reduced thoraco-lumbar spinal cord 5-HT by 84%). Taken together these data suggest that the only 5-HT agonist-induced behaviour mediated by the activation of 5-HT2 receptors located postsynaptic to bulbospinal 5-hydroxytryptaminergic (5-HTergic) neurones was back muscle contractions. 4. The wet-dog shake and forepaw licking behaviors produced by intrathecal CG 3509 (0.5 micrograms) were attenuated when ritanserin was administered intrathecally 30 min before, but not when it was given at the same time as CG 3509 and neither behaviour was altered by intrathecal 5,7-DHT. This suggests that bulbospinal 5-HTergic neurones are not involved in the production of these TRH analogue-induced behaviours and that the 5-HT2 receptors which mediate these behaviours are not located in the spinal cord.
Fone
K C
KC
Department of Physiology and Pharmacology, Queens Medical Centre, Nottingham.
Johnson
J V
JV
Bennett
G W
GW
Marsden
C A
CA
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000008:administration & dosage / Q000494:pharmacology; D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D008297:Male; D008732:Methoxydimethyltryptamines / Q000008:administration & dosage / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D008732:Methoxydimethyltryptamines; D011985:Receptors, Serotonin; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; C036430:orotirelin; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D013373:Substance P; D013973:Thyrotropin-Releasing Hormone