A direct comparison was made of the effects of serotonin 5‐HT1A and 5‐HT1B selective compounds on the spontaneous firing rate of dorsal raphe serotoninergic neurons in chloral‐hydrate‐anesthetized rats. Following intravenous administration, the 5‐HT1A selective compounds ipsapirone (TVX Q 7821) and LY 165163 potently inhibited single‐unit activity in a dose‐dependent manner whereas the 5‐HT1B 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‐HT1A 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‐HT1B 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‐HT1A compounds on these membrane properties exceeded those of 5‐HT. In summary, dorsal raphe 5‐HT neurons appear highly responsive to 5‐HT1A, but not to 5‐HT1B compounds; these findings are discussed with regard to the 5‐HT receptor subtypes as candidates for the somatodendritic autoreceptor of dorsal raphe neurons.
Synapse – Wiley
Published: Jan 1, 1987
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