Microdialysis in freely moving mice: determination of acetylcholine, serotonin and noradrenaline release in galanin transgenic mice

In the present study, we describe micro-surgical methods for simultaneous i mplantation of a microdialysis probe and an intraventricular injection cann ula via their respective guide cannulas into the mouse brain. Basal and sti mulated release of acetylcholine (ACh), serotonin (5-HT) and noradrenaline (NA) was determined in the ventral hippocampus. of freely moving mice. NA a nd 5-HT were determined in one ran by a newly developed HPLC method based o n precolumn. derivatization with benzylamine and fluorescence detection. Th e mice with a loss-of-function mutation of the galanin gene (KO) and the mi ce that over-expressed galanin (OE) were studied. No significant difference s in basal, potassium-stimulated or scopolamine-induced extracellular ACh l evels were observed in 4-month-old wild-type (WT) and KO mice. In the aged, 10-month-old animals, the basal extracellular ACh levels were significantl y reduced in both WT and KO groups. Galanin (I nmol i.c.v.) caused a signif icant reduction of basal extracellular NA by about 40% in both WT and galan in OE mice, however, in the latter group the effect was delayed by almost 2 h. A 10-min forced swimming stress caused a higher increase in release of NA and 5-HT in the OE group than in the corresponding WT mice. Finally, ven lafaxin (10 mg/kg i.p.) increased extracellular NA to 400% of the control v alues in the CBA mice, but only to 250% in the C57BL mice. It is concluded that galanin may play an important role in the cholinergic mechanisms under lying cognitive disorders. Furthermore, modulation by galanin and by behavi oral activation, of NA and 5-HT neurotransmission in galanin over-expressin g mice indicates its possible role in the aetiology of mood disorders. (C) 2001 Elsevier Science B.V. All rights reserved.