Electrocortical changes induced by perfusion of catecholamines into the brainstem reticular formation

Abstract

Various concentrations of noradrenaline and related catecolamines were perfused bilaterally into the pontine and mesencephalic reticular formation using push-pull cannulae. The initial effect of a 5-min perfusion of (-)-noradrenaline, (-)-adrenaline, (-)-phenylephrine or α-methyl noradrenaline, was to induce a two stage change in the electrocortical activity, that is, phasic followed by tonic desynchronisation. When high concentrations of these substances were used, a secondary sedative effect correlated with the appearance of slow wave (2–4 Hz) activity in the electrocorticogram was observed. In contrast, (-)-isoproterenol, even in high concentrations, did not produce secondary sedative effects. Using tritium labelled (±)-[7- 3H]-noradrenaline in the 10 −6 to 10 −3 m concentration range, it was established that the total amount of drug diffusing into the brain tissue was very low. The appearance of phasic electrocortical changes correlated with 0·4–25 ng noradrenaline (base) within the brain at the end of each cannula. Tonic electrocortical desynchronization which appeared when 9 × 10 −5 m to 7 × 10 −4 m solutions were used, gave tissue levels of exogenous noradrenaline (base) of 6·5–103 ng. Secondary sedative effects were usually observed with tissue levels in excess of 98 ng at the end of each cannula.