On a possible dual role for the lateral septal area 5-HT 1A receptor system in the regulation of water intake and urinary excretion

Abstract

The 5-hydroxytryptamine (5-HT) 1A receptor system plays a prominent role in a variety of physiological functions and behavior and regulation of this responsiveness of the receptor system has been implicated in the central regulation of water intake and urinary excretion. The lateral septal area (LSA) exhibits a high density of 5-HT 1A receptors, as well as a subpopulation of oxytocin (OT) receptors. Here we report the effects of pMPPF (a selective 5-HT 1A antagonist), d(CH 2) 5[Tyr(Me) 2Thr 4, Orn 5, Tyr(NH 2) 9]-vasotocin (an OT antagonist), and that 5-HT 1A receptor system is regulated as a consequence of activation of the Na + channel by veratridine. Cannulae were implanted into the LSA of rats to enable the introduction of the drugs. Injections of 8-OH-DPAT (a 5-HT 1A agonist) blocked water intake and increased urinary excretion, while pMPPF or the OT antagonist injected bilaterally before 8-OH-DPAT blocked its inhibitory effect on water intake and its diuretic effect. In contrast, increases in extracellular sodium levels induced by the sodium channel modulator, veratridine, enhanced 5-HT 1A responsiveness for water intake and reduced the diuretic effects induced by 8-OH-DPAT. These trials demonstrated that the responsiveness of the 5-HT 1A receptor system in the LSA can be enhanced or depressed as a consequence of an induced rise in extracellular sodium.