PRESYNAPTIC DISPLACEMENT OF SEROTONIN BY ALPHA-METHYL-5-HYDROXYTRYPTAMINE IN THE NUCLEUS-TRACTUS-SOLITARIUS OF THE RAT

Rat brain slices containing the nucleus tractus solitarius loaded with [H-3]5-hydroxytryptamine ([H-3]5-HT) for superfusion were stimulated at (3 Hz, 25 mA, 1 min) resulting in fractional release ratios S-2/S-1 of 0.89 for [H-3]5-HT in the presence of the serotonin uptake inhibit or 1.0 mu M 6-nitroquipazine (6-NQ). alpha-Methylserotonin (alpha-Me-5 -HT; 1.0 mu M), a non-selective 5-HT1 and 5-HT2 receptor agonist, sign ificantly reduced the S-2/S-1 ratio of [H-3]5-HT without affecting the basal release ratios B-2/B-1 1.00 +/- 0.04. Without 6-NQ in the perfu sion medium 1.0 mu M alpha-Me-5-HT sharply increased the basal release B-2/B-1 to 2.21 (P < 0.01). In low Ca2+ medium the S-2/S-1 ratio was reduced to 0.06 and alpha-Me-5-HT promoted a B-2/B-1 release of 2.17 ( P < 0.01). The 5-HT3 antagonist LY-278,584 did not block alpha-Me-5-HT induced basal release of [H-3]5-HT. Both pindolol and LY-53,857 block ed the autoinhibitory effects of alpha-Me-5-HT, but only LY-53,857 and 6-NQ blocked the basal release induced by alpha-Me-5-HT. These result s suggest that alpha-Me-5-HT reduces neurotransmitter release through the serotonin autoreceptor and displaces serotonin through a non-exocy totic release mechanism.