Neuronal responses to noradrenaline in the cerebral cortex: evidence against the involvement of alpha 2-adrenoceptors.

The technique of microelectrophoresis was used to test the hypothesis that alpha 2-adrenoceptors are involved in mediating the excitatory responses of single neurones to noradrenaline in the somatosensory cerebral cortex of the rat. In the first series of experiments the effects of two alpha 2-adrenoceptor antagonists, yohimbine and idazoxan (RX-781094), were compared on excitatory responses to noradrenaline, phenylephrine and acetylcholine. The response to noradrenaline was not more susceptible to antagonism by these drugs than the response to the alpha 1-adrenoceptor stimulant, phenylephrine. Yohimbine antagonized responses to all three agonists equally, while idazoxan antagonized responses to noradrenaline and phenylephrine equally with relative preservation of responses to acetylcholine. In the second series of experiments the effects of the selective alpha 2-adrenoceptor stimulant, UK-14304, were examined. UK-14304 produced weak and inconsistent excitations on a small number of cells; however, most of the cells did not respond to this drug. When applied continuously using low ejection currents, UK-14304 selectively and reversibly antagonized responses to noradrenaline and phenylephrine without affecting responses to acetylcholine. These results suggest that, in the somatosensory cortex of the rat, neuronal excitation to noradrenaline is unlikely to be mediated either wholly or partly by alpha 2-adrenoceptors. The antagonism of neuronal responses to noradrenaline and phenylephrine by idazoxan probably reflects the alpha 1-adrenoceptor antagonistic properties of the drug which is known to occur at higher concentrations. The low agonistic potency of UK-14304 and the antagonism of responses to noradrenaline and phenylephrine by UK-14304 suggest that this drug, like clonidine, may act as a partial agonist at alpha-adrenoceptors.