Evidence that exogenous but not endogenous norepinephrine activates the presynaptic alpha-2 adrenoceptors on serotonergic nerve endings in the rat hypothalamus

Abstract

In superfused rat hypothalamic slices, clonidine, norepinephrine (NE) and 6-fluoronorepinephrine 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 alpha-2 adrenoceptors and it was antagonized by the alpha adrenoceptor antagonists phentolamine or RX 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 RX 781094 modified the stimulation-evoked release of [3H]-5-HT at concentrations 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 still unable to modify the electrically evoked release of [3H]-5-HT. It is concluded that presynaptic alpha-2 adrenoceptors present on serotonergic nerve endings in the hypothalamus are not activated by endogenous NE and do not seem to play a physiological role in the regulation of serotonergic neurotransmission. However, presynaptic inhibitory alpha-2 adrenoceptors can be acted upon by exogenous agonists to inhibit 5-HT release. On the other hand, the presynaptic alpha-2 adrenoceptors on noradrenergic nerve terminals in the rabbit and rat hypothalamus are acted upon by released NE because the alpha-2 adrenoceptor antagonists by themselves increase the electrically evoked release of [3H]NE.