Serotonin modulates hypothalamic neuronal activity

Effects of serotonin (5-HT) on electrophysiological activities of single hypothalamic arcuate neurons in rat brain slices were observed by extracellular recording. The results showed that (1) of 385 arcuate neurons observed, the patterns of spontaneous firing were divided into 3 categories: "slow irregular" (46.0%), "fast continuous" (22.6%), and "bursting" firing (31.4%); (2) of 149 neurons tested for 5-HT, most (55.0%) responded to the drug by decreasing firing rate, 22.2% by increasing firing rate, 11.4% exhibit biphasic pattern, and 11.4% did not respond to 5-HT application; (3) substitution of low Ca²-high Mg²⁺ artificial cerebrospinal fluid (ACSF) for normal ACSF did not abolish the 5-HT-induced excitatory effect while it did abolish the 5-HT-induced inhibitory effect, suggesting the effect in latter cases was elicited by a Ca ²⁺-dependent release of neuroactive substances; (4) cyproheptadine, a non-selective 5-HT receptor antagonist, antagonized the 5-HT-induced excitatory effect in all neurons tested, while pindolol, a 5-HT_1A/1B receptor antagonist, antagonized the 5-HT-induced excitatory effect in 50% of neurons tested; (5) both cyproheptadine and pindolol antagonized the 5-HT-induced inhibitory effect; and (6) bicuculline, a GABA_A receptor antagonist, antagonized the 5-HT-induced inhibitory effect. These results suggest that 5-HT may exert its excitatory effects directly through 5-HT_1A/1B and other subtypes of 5-HT-receptors located on the surface of the neurons recorded, while its inhibitory effects are mediated indirectly through the activation of a local inhibitory GABAergic interneuron.