Yohimbine affects the evoked overflow of neurotransmitters from rat brain slices by more than one mechanism.

Abstract

Both yohimbine (0.1-10 microM) and phentolamine (10 microM) increased the tritium overflow evoked by electrical stimulation (3 Hz, 2 ms, 18 mA for 120 s every 20 min) of rat brain cortex slices previously incubated with [3H](-)-noradrenaline. At their maximally effective concentrations, neither of these compounds produced an effect which was fully maintained over the 1 h of the experiment, but the decline in effect of yohimbine (1.25 microM) was more marked, falling sharply to reach, after 1 h, 25% of the effect observed after 20 min, whereas phentolamine only declined to 60% of the effect after 20 min. In rat brain cortex slices previously incubated with [3H]5-hydroxytryptamine ([3H]5-HT), the tritium overflow evoked by electrical stimulation (3 Hz, 2 ms, 40 mA for 120 s) was increased by yohimbine (0.1-1 microM) and phentolamine (0.1-10 microM), but a higher concentration of yohimbine (10 microM) decreased evoked overflow below the levels seen in the absence of either drug. It is concluded that, at concentrations effective in inhibiting the presynaptic alpha-adrenoceptor-mediated mechanisms controlling transmitter release in rat brain slices, a non-alpha-adrenoceptor-mediated, possible local anaesthetic, action of yohimbine contributes to the overall effect of this drug on transmitter overflow.