Dopamine modulates neuronal excitability pre- and post-synaptically in the rat subfornical organ.

The aims of this study were to investigate the involvement of dopamine (DA) in drinking behaviour related to body fluid balance. All experiments were performed in rats. Water intake induced by intracerebroventricular injection of angiotensin II (ANGII) was suppressed by co-injection of DA in a dose-dependent manner. RT-PCR revealed the presence of mRNAs for all known DA receptors, D1-D5, in the subfornical organ (SFO), a brain region that plays a key role in regulating drinking behaviour. Extracellular recordings and whole-cell patch-clamp recordings from SFO neurons showed that DA or the D4 selective agonist PD168077 inhibited spontaneous electrical activity. The D4 antagonist L745870 blocked DA-induced inhibition of spontaneous electrical activity in SFO neurons. Under conditions of synaptic blockade, the inhibitory effects of DA and PD168077 still remained, but the D2/D3 agonist quinpirole and the D1/D5 agonist SKF38393 had almost no effect on electrical activity. While DA induced excitation in a small number of neurons, these excitatory responses almost disappeared following synaptic blockade. All neurons with firing rates that were suppressed by DA were excited by ANGII. In voltage clamp mode, we found that DA and quinpirole, but not SKF38393, suppressed GABAergic miniature inhibitory post-synaptic currents. These results suggest that DA inhibits neuronal activity in ANGII-sensitive SFO neurons primarily through the postsynaptic D4 receptor subtype. This may be a cause of the suppression of ANGII-induced water intake by DA. In addition, the inhibitory DA responses in SFO neurons may be modulated by presynaptic suppression of GABAergic inhibitory inputs through D2/D3 receptor subtypes.

Effect of central nicotinic activation on drinking behavior.

Intracerebroventricular injections of angiotensin II (ANG) and nicotine activate the subfornical organ (SFO), an essential central nucleus for ANG-induced drinking. Nicotine has been, however, reported to induce little drinking behavior. To clarify this paradox, we investigated effects of nicotine and ANG on activity of SFO neurons and drinking behavior. In extracellular recordings many SFO neurons (57%) were excited by the both drugs. The nicotine-induced excitation was transient, whereas the ANG-induced was long-lasting. After intracerebroventricular injection of nicotine, the latency to drinking was dose-dependently shortened, but the drinking volumes were much smaller than those by ANG. These suggest that central nicotinic activation contributes to induction of drinking behavior while drinking volume is small because effects of nicotine on neurons are short-lasting.

Central injection of galanin inhibits angiotensin II-induced responses in rats.

Galanin inhibits electrical activation of angiotensin II-sensitive neurons in the subfornical organ, which is related to angiotensin II-induced drinking behavior and pressor responses. In this study, the authors investigated whether intracerebroventricular injection of galanin in conscious rats inhibits the responses. Water intake following intracerebroventricular injection of angiotensin II at 100 pmol was inhibited significantly by coinjection of galanin at over 25 pmol, although galanin alone did not affect water intake. Furthermore, angiotensin II-induced pressor responses were inhibited significantly by coinjection of galanin at 50 pmol while galanin alone elicited slight pressor responses. These results suggest that galanin inhibits angiotensin II-induced physiological responses.

Intraperitoneal injection of pilocarpine activates neurons in the circumventricular organs and hypothalamus in rats.

It has been suggested that while the sialogogue pilocarpine elicits salivary secretion by acting directly on acinar cells of the salivary glands, it induces drinking behavior by acting on muscarinic receptors in the central nervous system. To study which brain regions are affected by the peripherally injected pilocarpine, we investigated changes in the numbers of c-Fos immunoreactive cells. The injections increased the numbers of c-Fos immunoreactive cells in the subfornical organ, median nucleus of preoptic area, organum vasculosum of lamina terminalis, paraventricular nucleus and supraoptic nucleus. Intracerebroventricular injection of pilocarpine produced similar changes in the expression of c-Fos immunoreactivity. The increases in immunoreactive expression induced by both the intraperitoneally and intracerebroventricularly injected pilocarpine were suppressed by previous intracerebroventricular injection of the muscarinic receptor antagonist atropine. Electrophysiological experiments using slice preparations and whole cell recordings showed that pilocarpine depolarized the membrane of neurons in the subfornical organ and suppressed the inhibitory GABAergic synaptic currents by a presynaptic action. The results suggest that peripherally applied pilocarpine does not act only on the salivary glands as a sialogogue, but also evokes thirst sensation by acting on the center controlling body fluid balance in the central nervous system.