Electrophysiological responses of serotoninergic dorsal raphe neurons to 5‐HT_1A and 5‐HT_1B agonists

<jats:title>Abstract</jats:title><jats:p>A direct comparison was made of the effects of serotonin 5‐HT<jats:sub>1A</jats:sub> and 5‐HT<jats:sub>1B</jats:sub> selective compounds on the spontaneous firing rate of dorsal raphe serotoninergic neurons in chloral‐hydrate‐anesthetized rats. Following intravenous administration, the 5‐HT<jats:sub>1A</jats:sub> selective compounds ipsapirone (TVX Q 7821) and LY 165163 potently inhibited single‐unit activity in a dose‐dependent manner whereas the 5‐HT<jats:sub>1B</jats:sub> selective compounds, m‐chlorophenylpiperazine (mCPP) and trifluoromethylphenylpiperazine (TFMPP), displayed only weak or irregular actions. Low microiontophoretic currents of ipsapirone and LY 165163 were also effective in suppressing spontaneous firing; dose‐response relationships for the 5‐HT<jats:sub>1A</jats:sub> compounds were indistinguishable from that of 5‐HT itself. In contrast, dorsal raphe neurons were only weakly responsive to microiontophoretic application of mCPP and TFMPP; dose‐response relationships for the 5‐HT<jats:sub>1B</jats:sub> compounds were significantly displaced from that of 5‐HT. In intracellular studies, ipsapirone and LY 165163, when added to the media bathing brain slices, mimicked the actions of 5‐HT in hyperpolarizing dorsal raphe cell membranes and decreasing input resistance; however, the maximal effects of the 5‐HT<jats:sub>1A</jats:sub> compounds on these membrane properties exceeded those of 5‐HT. In summary, dorsal raphe 5‐HT neurons appear highly responsive to 5‐HT<jats:sub>1A</jats:sub>, but not to 5‐HT<jats:sub>1B</jats:sub> compounds; these findings are discussed with regard to the 5‐HT receptor subtypes as candidates for the somatodendritic autoreceptor of dorsal raphe neurons.</jats:p>