DISPLACEMENT OF NOREPINEPHRINE BY ALPHA-METHYLNOREPINEPHRINE IN THE NUCLEUS-TRACTUS-SOLITARIUS OF THE RAT

Rat brain slices from the dorsomedial medulla containing the nucleus t ractus solitarius were loaded with [H-3]norepinephrine ([H-3]NE) for s uperfusion. Electrical stimulation (3 Hz, 25 mA, 1 min) resulted in fr actional release ratios S-2/S-1 Of 0.97 +/- 0.02 in normal Krebs-Hense leit (KH) and 0.93 +/- 0.06 in the presence of 30 mu M cocaine. With c ocaine in the KH medium, L-alpha-methylnorepinephrine (alpha-MeNE) sig nificantly reduced the [H-3]NE release S-2/S-1 without affecting the b asal release ratios, Without cocaine in the KH medium both 0.1 and 1.0 mu M alpha-MeNE increased the basal release B-2/B-1 that was not affe cted by yohimbine. Prazosin had no effect on the S-2/S-1 ratio but did attenuate the basal release effects of alpha-MeNE. In low Ca2+ studie s where the S-2 stimulus was abolished, 1.0 mu M alpha-MeNE induced a sharply elevated increase in the B-2/B-1 ratio. It appears that alpha- MeNE in the presence of the uptake inhibitors reduces presynaptic neur otransmitter release through alpha(2)-adrenoceptors, whereas when upta ke of the monoamines was not blocked alpha-MeNE was considerably more efficacious asa displacing agent of neurotransmitter.