Electrophysiological effects of methylphenidate on the coeruleo-cortical noradrenergic system in the rat.

The effect of methylphenidate on noradrenergic neurotransmission was investigated in urethane-anesthetized rats. The spontaneous activity of locus coeruleus noradrenergic neurons was the same in rats treated for 7 days with methylphenidate as in the controls. In control rats, i.v. methylphenidate induced a reduction of locus coeruleus neuronal firing whereas in rats treated for 7 days with methylphenidate, the same dose of methylphenidate failed to induce any change in locus coeruleus activity. At this time, clonidine induced a lesser reduction of locus coeruleus neuronal firing than in the controls, indicating that their autoreceptors had become desensitized. Following electrical stimulation of the locus coeruleus, most of the spontaneously firing cortical neurons were inhibited but the percentage of such neurons was reduced and the neurons showed a decreased responsiveness after methylphenidate treatment. The responsiveness of cortical neurons to microiontophoretic applications of NA as assessed by the I.T50 method was reduced after 7 days of treatment with methylphenidate. These findings suggest that the efficacy of cortical NA neurotransmission is markedly reduced following methylphenidate treatment.