Effects of repeated treatment with 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on the autoregulatory control of dorsal raphe 5-HT neuronal firing and cortical 5-HT release.

These experiments were designed to examine the effects of repeated 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) treatment on the autoregulatory control of cortical 5-HT release and dorsal raphe nucleus (DRN) 5-HT neuronal cell firing. Repeated DOI treatment decreased the behavioural responsiveness (wet-dog shakes) of 5-HT2 receptors and attenuated the inhibitory effects of the 5-HT1A receptor agonist, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), on both cortical 5-HT release and DRN 5-HT neuronal firing. In contrast, the inhibitory effect of acute DOI on cortical 5-HT release and DRN 5-HT neuronal firing was unaffected by repeated DOI treatment. The results demonstrate that changes in the responsiveness of 5-HT2 receptor function may influence the responsiveness of presynaptic 5-HT1A receptors regulating 5-HT neuronal function. The results also provide further evidence that the inhibition of cortical 5-HT release and DRN 5-HT neuronal firing produced by DOI is not mediated by 5-HT2 receptor activation.