Comparative behavioural profile of centrally administered tachykinin NK1, NK2 and NK3 receptor agonists in the guinea‐pig

1 The NK, tachykinin receptor agonists, septide, [Sar9, Met(O2)11]SP and [Pro9]SP produced locomotor hyperactivity (10–20 min) when injected intracerebroventricularly (i.c.v.) in the guinea‐pig. Producedlocomotor The most potent in eliciting this hyperactivity was septide (from 0.63 to 5 μg), compared to [Sar9, Met(O2)11]SP, which was active at 2.5 and 5 μg and [Pro9]SP which induced a non‐significant increase even at 10 μg. 2 Wet‐dog shakes were elicited by septide, [Sar9, Met(O2)11]SP and [Pro9]SP injected by the i.c.v. route in the guinea‐pig. [Sar9, Met(O2)11]SP, active from 0.16 to 2.5 μg was more potent than septide (active at 1.25 μg) and [Pro9]SP (active at 0.63 μg) in eliciting such behaviour. To a lesser extent, grooming was also observed after injection of these agonists. 3 The NK2 tachykinin receptor agonist, [Lys5, MeLeu9, Nle10]NKA(4–10), up to the dose of 10 μg i.c.v. had no effect in the guinea‐pig. It neither modified locomotor activity nor induced a characteristic behavioural response. At higher doses (20μg), some toxic effects were noted. 4 The NK3 tachykinin receptor agonist, senktide, contrasts with the NK1 receptor agonists in that it elicited only wet‐dog shakes, at doses ranging from 0.32 to 1.25 μg. It neither modified locomotor activity (1 pg) nor induced grooming (up to 5 μg) in the guinea‐pig. 5 To our knowledge, these results are the first demonstration that the guinea‐pig could be useful to differentiate tachykinin agonists on the basis of their behavioural profile, distinct from those obtained in mice and rats.