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.

Neuronal effects of neurokinin B on the rat subfornical organ.

The subfornical organ is an essential central nucleus for angiotensin II-induced body fluid regulation. Similar to angiotensin II, centrally injected neurokinin B (NKB) may induce cardiovascular responses by the subfornical organ; however, it does not induce water intake. To clarify this inconsistency, we investigated the neuronal effects of NKB on subfornical organ neurons in slice preparations along with its behavioral effects in vivo. In electrophysiological extracellular recordings, NKB excited angiotensin II-insensitive and inhibited angiotensin II-sensitive neurons. Centrally injected NKB inhibited peripherally injected angiotensin II-induced water intake. These results suggest that NKB-mediated neuronal effects on the subfornical organ are likely to be involved in antidipsogenic responses in addition to the previously reported cardiovascular responses.

Cell subpopulations of nicotine-sensitive subfornical organ neurons in rat.

The subfornical organ (SFO), which is related to drinking and cardiovascular regulation, is activated by central application of nicotine (NIC) and angiotensin II (ANG). However, NIC-induced drinking is much smaller than ANG-induced one although approximately 60% of SFO neurons are affected by both NIC and ANG. Therefore, some specific subpopulations of SFO neurons for NIC or ANG may be related to such different drinking responses. To clarify subpopulations of NIC-sensitive neurons, electrophysiological properties of SFO neurons with the application of NIC was investigated at whole-cell patch-clamp recordings. Based on our developed electrophysiological criteria of the recovery kinetics of tetraethylammonium-resistant transient outward K(+) currents, two sub-types (F- and S-type neurons) were distinguished. Twenty-nine dissociated SFO neurons were examined to determine whether they showed NIC-induced inward currents. Most F-type neurons (n=19/21) showed NIC sensitivity, but most S-type neurons (n=7/8) did not. Our previous study had demonstrated that half of the F-type and all of the S-type units showed ANG sensitivity. These suggests that almost all of the NIC-sensitive SFO neurons were electrophysiologically classified as the F-type, but not S-type, and this differs in part from angiotensin sensitivity. The different subpopulations for chemical sensitivities in the SFO may be related to different drinking responses.