Abstract:
:The purpose of the present study was to confirm the functional regulation by alpha 2-adrenoceptors of the release of serotonin (5-HT) from the rat hippocampus in vivo. Under several pharmacological conditions, extracellular levels of 5-HT were estimated by assaying its concentrations in the perfusate by high performance liquid chromatography with electrochemical detection. Extracellular 5-HT in the hippocampus was reduced by tetrodotoxin (10 microM) co-perfusion, but increased by perfusion of a selective 5-HT re-uptake inhibitor, fluoxetine (10 microM). Addition of potassium (K+, 120 mM) to the perfusion fluid evoked an approximately 3-fold increase in 5-HT release. When the alpha 2-adrenoceptor agonist UK14,304 (0.1-10 microM) was added to the perfusion solution, the K(+)-evoked 5-HT release was significantly inhibited in a concentration-dependent manner. This inhibitory action of UK14,304 was reversed by pretreatment with an alpha 2-adrenoceptor antagonist, idazoxan (5 mg/kg, i.p.). In rats which were catecholaminergically denervated with 6-hydroxydopamine, UK14,304 (10 microM) still inhibited the K(+)-evoked 5-HT release. Treatment with pertussis toxin (PTX) did not alter the K(+)-evoked release of 5-HT but abolished the inhibitory effect of UK14,304. These findings suggest that 5-HT release is functionally modulated via alpha 2-adrenoceptors located on the serotonergic nerve terminals in the rat hippocampus and furthermore, the possibility that the inhibitory of alpha 2-adrenoceptors is linked to G-proteins which are substrates of PTX.
journal_name
Neurosci Lettjournal_title
Neuroscience lettersauthors
Numazawa R,Yoshioka M,Matsumoto M,Togashi H,Kemmotsu O,Saito Hdoi
10.1016/0304-3940(95)11635-asubject
Has Abstractpub_date
1995-06-16 00:00:00pages
161-4issue
3eissn
0304-3940issn
1872-7972pii
030439409511635Ajournal_volume
192pub_type
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