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-mu-g), sumatriptan (10-25-mu-g) and RU24969 (25-mu-g) 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-mu-g) 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-mu-g) and the 5-HT3 receptor agonist, 2-methyl 5-HT (2-Me5-HT, 25-mu-g) were without effect. 3 The contralateral rotation induced by 5-CT (10-mu-g) 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-mu-g) and sumatriptan (2-mu-g) 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-HT1D receptor activation but definitive classification of the receptor will not be possible until selective 5-HT1D-antagonists become available. This may therefore represent the first model to study this receptor subtype in vivo.