Central administration of 5‐HT activates 5‐HT1A receptors to cause sympathoexcitation and 5‐HT2/5‐HT1C receptors to release vasopressin in anaesthetized rats

Abstract

The effects of intracerebroventricular injections to the right lateral ventricle (i.c.v.) of 5‐hydroxytryptamine (5‐HT, 40 and 120 nmol kg−1), N,N‐di‐n‐propyl‐5‐carboxamidotryptamine (DP‐5‐CT; 3 nmol kg−1), 5‐carboxamidotryptamine (5‐CT; 3 nmol kg−1), 8‐hydroxy‐2‐(di‐N‐propylamino) tetralin (8‐OH‐DPAT; 3, 40 and 120 nmol kg−1) and 1‐(2,5‐di‐methoxy‐4‐iodophenyl)‐2‐aminopropane (DOI; 40 and 120 nmol kg−1) on renal sym pathetic nerve activity, blood pressure, heart rate and phrenic nerve activity were investigated in normotensive rats anaesthetized with α‐chloralose. 5‐HT caused a long lasting pressor response which was associated with an initial bradycardia and renal sympathoinhibition followed by a tachycardia and renal sympathoexcitation. Pretreatment with the 5‐HT2/5‐HT1C receptor antagonists, cinanserin (300 nmol kg−1, i.c.v.) or LY 53857 (300 nmol kg−1, i.c.v.) reversed the initial bradycardia and sympathoinhibition to tachycardia and sympathoexcitation. Combined pretreatment with LY 53857 (300 nmol kg−1, i.c.v.) and the 5‐HT1A antagonist, spiroxatrine (300 nmol kg−1, i.c.v.), blocked the effects of 5‐HT on all the above variables. Pretreatment with the vasopressin V1‐receptor antagonist, β‐mercapto‐β,β‐cyclopentamethylenepropionyl1, O‐Me‐Tyr2, Arg8‐vasopressin [(d(CH2)5Tyr(Me)AVP, 10 μg kg−1, i.v.] did not affect the magnitude but reduced the duration of the pressor response produced by i.c.v. 5‐HT and reversed the initial bradycardia and renal sympathoinhibition to tachycardia and sympathoexcitation. 1‐(2,5‐Di‐methoxy‐4‐iodophenyl)‐2‐aminopropane (DOI) caused a pressor effect which was associated with a bradycardia and sympathoinhibition. These effects were blocked by pretreatment with BW501C67 (0.1 mg kg−1, i.v.), a peripherally acting 5‐HT2/5‐HT1C receptor antagonist. However, BW501C67 (0.1 mg kg−1, i.v.) failed to block the effects of i.c.v. 5‐HT. DP‐5‐CT, 5‐CT and 8‐OH‐DPAT (3 nmol kg−1, i.c.v.) caused sympathoexcitation, tachycardia and a rise in blood pressure. Pretreatment with methiothepin (1 mg kg−1, i.v.) or spiroxatrine (300 nmol kg−1, i.c.v.) attenuated the response to i.c.v. DP‐5‐CT. It is concluded that i.c.v. administration of 5‐HT activates 5‐HT1A receptors to cause sympathoexcitation and 5‐HT2 or 5‐HT1C receptors to cause the release of vasopressin. 1992 British Pharmacological Society