Alterations in beta adrenergic physiological response characteristics after long-term treatment with desmethylimipramine: interaction between norepinephrine and gamma-aminobutyric acid in rat cerebellum.

Changes in beta adrenergically mediated responses of cerebellar Purkinje cells to norepinephrine (NE) were assessed in rats chronically treated with desmethylimipramine (DMI). A decreased efficacy of NE action after DMI pretreatment was manifested in both a higher mean iontophoretic current dose of the catecholamine required to induce threshold depressions of Purkinje cell spontaneous activity and a markedly diminished ability of NE to enhance inhibitory responses to gamma-aminobutyric acid. No significant differences were found in the responsiveness of Purkinje cells to gamma-aminobutyric acid alone between control and DMI-pretreated animals. However, in a significant portion of the Purkinje cells tested in the DMI-pretreated group, concurrent NE application resulted in an antagonism rather than an enhanced responsiveness to gamma-aminobutyric acid. The results of this electrophysiological study provide evidence for a "modulatory subsensitivity" toward noradrenergic actions in the cerebellum after a decrease in beta receptor number induced by prolonged treatment with DMI.