EVIDENCE THAT EXOGENOUS BUT NOT ENDOGENOUS NOREPINEPHRINE ACTIVATES THE PRESYNAPTIC ALPHA-2 ADRENOCEPTORS ON SEROTONERGIC NERVE-ENDINGS IN THE RAT HYPOTHALAMUS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 228  (3) , 725-732
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 [idazoxan]. 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. Presynaptic .alpha.2 adrenoceptors present on serotonergic nerve endings in the hypothalamus are evidently not activated by endogenous NE and do not seem to play a physiological role in the regulation of serotonergic neurotransmission. Presynaptic inhibitory .alpha.2 adrenoceptors can be acted upon by exogenous agonists to inhibit 5-HT release. 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.