Multiple receptor subtypes mediate the effects of serotonin on rat subfornical organ neurons

The subfornical organ (SFO) receives significant serotonergic innervation. However, few reports have examined the functional effects of serotonin on S FO neurons. This study characterized the effects of serotonin on spontaneou sly firing SFO neurons in the rat brain slice. Of 31 neurons tested, 80% re sponded to serotonin (1-100 mu M) with either an increase (n = 15) or decre ase (n = 10)in spontaneous activity. Responses to serotonin were dose depen dent and persisted after synaptic blockade. Excitatory responses could also be mimicked by the 5-hydroxytryptamine (5-HT)(2A/2C) receptor agonist 2,5- dimethoxy-4-iodoamphetamine (DOI; 1-10 mu M) and could be blocked by the 5- HT2A/2C-receptor antagonist LY-53,857 (10 mu M). LY-53,857 unmasked inhibit ory responses to serotonin in 56% of serotonin-excited cells tested. Seroto nin-inhibited cells were also inhibited by the 5-HT1A-receptor agonist 8-hy droxy-2(di-n-propylamino)tetralin (8-OH-DPAT; 1-10 mu M; n = 7). The data i ndicate that SFO neurons are responsive to serotonin via postsynaptic activ ation of multiple receptor subtypes. The results suggest that excitatory re sponses to serotonin are mediated by 5-HT2A or 5-HT2C receptors and that in hibitory responses may be mediated by 5-HT1A receptors. In addition, simila r percentages of serotonin-excited and -inhibited cells were also sensitive to ANG II. As such the functional relationship between serotonin and ANG I i in the SFO remains unclear.