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Evidence that the unilateral activation of 5‐HT 1D receptors in the substantia nigra of the guinea‐pig elicits contralateral rotation
Author(s) -
Higgins G.A.,
Jordan C.C.,
Skingle M.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12170.x
Subject(s) - ritanserin , agonist , metergoline , endocrinology , medicine , chemistry , 5 ht receptor , substantia nigra , receptor antagonist , pharmacology , zolmitriptan , receptor , dopaminergic , antagonist , serotonin , sumatriptan , dopamine
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‐HT 1 receptor agonists, 5‐carboxamidotryptamine (5‐CT) (2–25 μg), sumatriptan (10–25 μg) and RU24969 (25 μg) all induced a marked contralateral rotation. In contrast, the selective 5‐HT 1A receptor agonist 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH DPAT, 10–25 μg) produced only a very small response, whilst the selective 5‐HT 1C /5‐HT 2 receptor agonist (±)‐1‐(4‐iodo‐2,5‐dimethoxyphenyl)‐2‐aminopropane hydrochloride ((±)‐DOI) (25 μg) and the 5‐HT 3 receptor agonist, 2‐methyl 5‐HT (2‐Me5‐HT, 25 μg) were without effect. 3 The contralateral rotation induced by 5‐CT (10 μg) was attenuated following pretreatment with the non‐selective 5‐HT 1 /5‐HT 2 receptor antagonists methiothepin (1 mg kg −1 , s.c.) and metergoline (5–10 mg kg −1 , s.c.) but not the 5‐HT 1C /5‐HT 2 antagonist ritanserin (1 mg kg −1 , s.c.) or the 5‐HT 3 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 μg) and sumatriptan (2 μg) 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‐HT 1D receptor activation but definitive classification of the receptor will not be possible until selective 5‐HT 1D ‐antagonists become available. This may therefore represent the first model to study this receptor subtype in vivo .