Evidence that exogenous but not endogenous norepinephrine activates the presynaptic alpha,-adrenoceptors on serotonergic nerve endings in the rat hypothalamus

In superlused rat hypothalamic slices, clonidine, norepinephrine (NE) and 6-fluoronorepinephrie reduced the electrically evoked release of recently taken up [3H]-5-hydroxytryptamine (5-HT). The inhibitory action of these drugs involves the activation of presynaptic a!pha-2 adrenoceptors and it was antagonized by the alpha adrenoceptor antagonists phentolamine or AX 781094. In contrast to the facilitating effect of alpha-2 adrenoceptor antagonists on the electrically evoked [3H]NE overflow in rabbit hypothalamic slices, neither phentolamine nor AX 781 094 mod-ified the stimulation-evoked release of [3H]-5-HT at concentra-tions which completely antagonized the inhibitory action of NE, 6-fluoronorepinephrine and clonidine on 5-HT neurotransmission. In the presence of cocaine, which inhibits the neuronal uptake of NE and increases the concentration of this neurotransmitter in the synaptic gap, alpha-2 adrenoceptor antagonists were stil