The decrease in dorsal raphe S HT neuronal firing produced by the microiontophoretic application of DO1 was related to the ejection current with complete inhibition of firing seen at 90 nA. iscussion Systemic administration of DOI produced a marked dose related decrease in dorsal raphe 5 HT neuronal firing. DOI also decreased the firing rate of 5 HT neurones in the dorsal raphe . Furthermore, the results compare with those obtained with the 5 HT agonist 8 OH DPAT which following either systemic or intra raphe administration inhibits both 5 HT neuronal firing and cortical 5 HT release . The decrease in the firing rate on i.v. administration of DOM has been suggested to be related to large increases in blood pressure rather than as a direct action of DOM on the raphe neurones . In this study blood pressure was not monitored. However, the systemic administration of DO1 produced an extremely rapid decrease in the firing rate of 5 HT neurones in the dorsal raphe and m.c re surprisingly the return to the basal rate occurred quickly after the period of cessation.
These findings may suggest that the effect of DO1 on the firing rate of the dorsal raphe neurones is mediated indirectly by change in another system and this might account for the on oft effects observed. One possible explanation is that DO1 has local anaesthetic properties; however this would not adequately explain the present results as DO1 only inhibited the firing of identified 5 HT neurones and not other ceils. Local administration of DOI into the raphe also produced a Pazopanib price decrease in 54HT neuronal firing ir?dicating that the DOI mediated inhibition was due to a direct effect in the dorsal raphe nucleus. The administration of DOI directly into the frontal cortex did not decrease frontal cortical concentration of extracellular 5 HT unlike systemic administration, suggesting that the effect of DOI on frontal cortex 5 I R release is not due to an action within the frontal cortex itself.
However, when DO1 was administered locally into the dorsal raphe the concentration of extracellular 5 HT in the frontal cortex Entinostat decreased. This result suggests that the decrease in 5 HT release in the frontal cortex on systemic administration of DO1 is due to an action of DO1 within the dorsal raphe and may possibly result from the decrease in the firing rate of 5 HT neurones. The decrease in extracellular concen tration of 5 H F in the frontal cortex, however, occurred considerably after the decrease in the firing rate of the 5 H I? neurones in the dorsal raphe and persisted after the firing rate had returned to pre drug value. The percentage decrease in extracellular .5 HT in the frontal cortex was also smaller than that of the firing rate of the 5 HT neurones in the dorsal raphe.