It was also partly antagonized by a high concentration of imipramine reported a decrease in extracellular DOPAC levels following dorsal raphe stimulation whereas De Simoni et al. found an increase in DOPAC levels, but with no change in the level of 3 methoxytyramine. The interpretation of these studies is further complicated by the fact that the dorsal raphe also innervates the substantia nigra where it may influence the firing rate of at least a proportion of the nigro striatal DA cells . In conclusion, the results of the present study confirm previous endings that low concentrations of 54 R can enhance the release of label from DA loaded striatal tissue. Furthermore, 5 HT also enhances calcium evoked tritium release. These effects do not appear to be mediated by S EIT receptors on dopaminergic terminals, but rather involve the entry of 5 HT into the terminal. The studies were carried out with male Sprague Dawtry rats . Upon arrival in our animal quarters, animals were housed in groups of five per cage and kept under controlled environmental conditions for at least a week before being used in the experiments.
2.2. Drugs Chtoral hydrate , hydro 2 tctralin HBr OHDPAT, RBI, Natick, MA, U.S.A 2 l piperazinyl butyl 1,2 benzisothiazol 3 2H one l,l dioxide HCI and 8 ethyl S aspiro decane 7,9 dione 2 HCl were dissolved in saline and administered in a volume of 4 5 ml kg i.p. or 1 ml kg S.C 1 O 0Xmethylamino propyl l S phthalancarbonitrile . HBr was dissolved at a concentration of 1 PM in the artificial cerebrospinal fluid used as perfusion medium. Groups buy SP600125 of rats were given a single injection of vehicle or of the reference 5 HT receptor agonist 8 OH DPAT . These doses of S OH DPAT represent sub rn rna y , m mally and supramaximally effective levels for activation of somatodendritic 5 HT autoreceptors, based on previous studies . About 20 24 h after the vehicle g OH DPAT injection, the rats were anaesthetised with chloral hydrate . A hole was drilled in the skull bone, and an in vivo brain microdialysis probe .
The probe was perfused at a rate of 1 pl min with artificial CSF containing the 5 HT reuptake blocker citalopram . Dialysates were collected every 20 min post probe implantation and analysed for 5 HT contents by means of HPLC EC as the experiment progressed. After a control period to establish stable 5 HT baseline levels, either S OH DPAT , ipsapirone was administered S.C. as 5 HT screening compounds selleck chemicals receptor agonist challenge treatment. Sampling and HPLC EC analysis was then continued for a further 2 h. The 5 HT agonist induced inhibition of 5 HT release from the ventral hippocampus is likely to reflect the activation of somatodendritic SHT autoreceptors in the raphe, and the doses indicated of OH DPAT, ipsapirone and BMY 7378 are half maximally to milljmally effective in this respect and corresponding 8 OH DPAT pretreated groups .