Beer et al. found that bolus 8 OH DPAT pretreatment enhanced the dorsal raphe stimulation induced rise in 5 HIAA levels in the frontal cortex, and also tended to do so, although non significantly, in the rest of brain. However, since electrica stimulation of the dorsal raphe in all probability overrides receptor mediated influences exerted at the cell body level, 5 HT autoreceptor down regulation is unlikely to account for the change in stimulation efficiency observed by these authors. As an alternative explanation, it could be suggested that the modest increases in the baseline and in the stimulation evoked 5 HT activity indices in this condition involve changes at the terminal level. It is well established that S OH DPAT administration results in S HT autoreceptor mediated inhibition of 5 HT neuronal firing . Administration of a high dose of OH DPAT would be expected to elicit a relatively long lasting inhibition of 5 HT neuronal firing, accompanied by a reduction in the biophase 5 NT concentration.
Tentatively, this might in turn lead to an attenuated negative feedback suppression of presynaptic 5 HT synthesis, TAK-875 metabolism and possibly also release, and thus to enhanced I IT synaptic transmission, particularly after electrical stimulation. The present study does not exclude the ssibili that 8 OH DPAT pretreatment may differentially affect 5 HT autoreceptor responsiveness in different parts of the 5 HT cell body areas. The raphe nuclei have a distinct topographical organisation with respect to 5 HT ;Iutoreceptor density and projection patterns , and further measurements of regionally discrete terminal 5 HT release might thus be of interest of this context. With regard to the basal 5 HT autoreceptor agonist responsiveness, we have recently found that systemic 8 OH DPAT decreases dialysate levels of 5 HT in both median and dorsal raphe innervated areas, including the frontal cortex, nucleus accumbens, dorsal and ventral hippocampus, medial septum and globus pallidus .
With the possible exception of the latter area, these data provided little evidence to support the idea that brain peptide company 5 HT neuronal projections are heterogenous with respect to the 5 HT autoreceptor regulation of 5 HT release. In summary, the present study indicates that one day after single dose 8 OH DPAT administration there is no appreciable change in the functional responsiveness of 5 HT autoreceptors controlling the reIease of 5 HT in the ventral hippocampus, as studied by in vivo microdialysis in chloral hydrate anaesthetised rats. Taking into account the concomitant 25 reduction in raphe 5 HT radioligand binding sites described by others . and O, NtO mixture, and urethane 1.3 g kg i.p. in microiontophoretic experiments male Wistar rats the guide cannula was implanted in the dorsal raphe using a hydraulic microdrive.