Modulatory interactions between enkephalin and catecholamines: anatomical and physiological substrates.

The anatomical and electrophysiological basis of enkephalin-catecholamine interactions was studied in the central nervous system of the Sprague-Dawley rat. Sections of fetal rat brain were treated alternatively with antibodies raised against enkephalin or tyrosine hydroxylase (EC 1.14.16.2). Enkephalinergic fibers were found to innervate almost all brain areas known to contain catecholamine cell bodies or terminal fields. The possible electrophysiological correlates of such an overlap in enkephalin and catecholamine terminal fields was investigated in frontal neocortex. Parenteral administration of antipsychotic agents known to block catecholamine receptors, such as spiroperidol, alpha-flupenthixol, and (+)-butaclamol, reversibly antagonized enkephalin-induced depressions of neuronal activity. The biochemically inactive isomers of these antipsychotics, beta-flupenthixol and (-)-butaclamol, manifested no such activity. Unilateral lesions of the catecholaminergic projections to frontal cortex produced by interstitial injection of 6-hydroxydopamine resulted in an ipsilateral decrease in enkephalin efficacy and in an elimination of the antagonisms of enkephalin depressions by antipsychotic agents. It is hypothesized that catecholamines may act as modulators to augment responsiveness to peptides such as enkephalins.