The effects of dorsal raphe (DR) stimulation on neural activity in the rat lateral hypothalamic area (LHA), including specific glucose-sensitive neurons, were investigated by extracellular and intracellular recording in vivo, and the neurotransmitters involved were determined. 2. In 67 adult male anesthetized rats, 287 extracellular and 49 intracellular recordings of LHA responses to electrical stimulation of the DR were examined. 3. To determine neurotransmitter candidates, the effects of serotonin and the serotonin antagonists methysergide, lisuride, and (-)-propranolol were investigated by systemic administration and microelectrophoresis. 4. Of 287 spontaneously firing LHA neurons tested by DR stimulation, 157 (55%) were inhibited. Among these, 51% were glucose sensitive. The serotonin 1 receptor antagonists, lisuride and (-)-propranolol, attenuated the inhibitory responses to both DR stimulation and electrophoretic serotonin application. 5. Seventy-three (25%) were excited by DR stimulation, and 71% of these were glucose insensitive. Methysergide attenuated the excitatory responses to DR stimulation and the inhibitory response to electrophoretic serotonin application, but (-)-propranolol did not attenuate the excitation. 6. Intracellular recordings of LHA neurons during DR stimulation showed monosynaptic excitatory postsynaptic potentials (EPSPs) or inhibitory postsynaptic potentials (IPSPs) with 3.8 and 3.0 ms latency, respectively. The reversal potential for the former was approximately -17 and for the latter, -94 mV. 7. From the results we concluded that 75% of LHA glucose-sensitive neurons receive inhibitory serotonin inputs from the DR through serotonin 1 receptors, and 20% of glucose-insensitive neurons receive excitatory inputs from the DR through serotonin 2 receptors though 41% of these receive inhibitory inputs through serotonin 1 receptor.
