Evidence that the unilateral activation of 5-HT1D receptors in the substantia nigra of the guinea-pig elicits contralateral rotation.
1. The effects of various 5-hydroxytryptamine (5-HT) receptor agonists were examined following unilateral infusion into the substantia nigra (SN) of the guinea-pig. 2. The 5-HT1 receptor agonists, 5-carboxamidotryptamine (5-CT) (2-25 micrograms), sumatriptan (10-25 micrograms) and RU24969 (25 micrograms) all induced a marked contralateral rotation. In contrast, the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH DPAT, 10-25 micrograms) produced only a very small response, whilst the selective 5-HT1C/5-HT2 receptor agonist (+-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride ((+/-)-DOI) (25 micrograms) and the 5-HT3 receptor agonist, 2-methyl 5-HT (2-Me5-HT, 25 micrograms) were without effect. 3. The contralateral rotation induced by 5-CT (10 micrograms) was attenuated following pretreatment with the non-selective 5-HT1/5-HT2 receptor antagonists methiothepin (1 mg kg-1, s.c.) and metergoline (5-10 mg kg-1, s.c.) but not the 5-HT1C/5-HT2 antagonist ritanserin (1 mg kg-1, s.c.) or the 5-HT3 antagonist, ondansetron (0.5 mg kg-1, s.c.). An involvement of dopaminergic systems in the rotational response to 5-CT was implied by the antagonism of 5-CT-induced rotation by haloperidol (0.3 mg kg-1, s.c.). 4. At doses lower than those required to produce contralateral rotation, 5-CT (0.08-0.4 micrograms) and sumatriptan (2 micrograms) induced a small, but nonetheless consistent, ipsilateral rotation. 5. The data with agonists and antagonists taken together suggest that 5-CT-induced contralateral rotation may be mediated by 5-HTID receptor activation but definitive classification of the receptor will not be possible until selective 5-HTID-antagonists become available. This may therefore represent the first model to study this receptor subtype in vivo.
Higgins
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GA
Department of Neuropharmacology, Glaxo Group Research Ltd, Ware, Herts.
Jordan
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CC
Skingle
M
M
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D009068:Movement / Q000187:drug effects / Q000502:physiology; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D012399:Rotation; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D018170:Sumatriptan
D007211:Indoles; D011985:Receptors, Serotonin; D013449:Sulfonamides; D012701:Serotonin; D008719:Methiothepin; D018170:Sumatriptan; C047087:5-carboxamidotryptamine