α2-adrenoceptor activation increases a cationic conductance and spontaneous gabaergic synaptic activity in dopaminergic neurones of the rat substantia nigra

Noradrenaline (NA) plays an important role in compensating for the loss in dopaminergic (DA) function following lesions of the DA neurones of the substantia nigra (SN). alpha(2)-Adrenoceptors are largely expressed in these neurones, but the cellular response to their activation is unknown. Whole-cell patch-clamp recordings were made from DA neurones of rat SN. At a holding potential of -60 mV, bath application of NA (50 muM) induced an inward current (-20.3 +/- 10.0 pA) in 50% of the recorded neurones. This effect was mimicked by UK-14304 (50 muM), a specific alpha(2)-adrenoceptor agonist, whereas alpha(1)-adrenoceptor and P-adrenoceptor agonists failed to induce a response. Surprisingly, alpha(2)-adrenoceptor antagonists (idazoxan, RX-811059, SKF-86466 and yohimbine) also induced an inward current that could occlude the one induced by UK-14304, suggesting that they may act as alpha(2)-adrenoceptor agonists. The inward current results from an increase in cationic conductance identical to the one previously described in these neurones, as neurotensin (1 muM), known to activate it, occluded the inward current induced by UK-14304. In addition, GABAergic miniature inhibitory postsynaptic current frequency was increased by activation of presynaptic alpha(2)-adrenoceptors. We conclude that the effects of NA on alpha(2)-adrenoceptors can contribute to the previously described composite action of NA on DA neurone firing and can be pharmacologically differentiated from the effect of NA on DA and neighbouring neurones known to be mediated through alpha(1)-adrenoceptors. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.