Chronic treatment with lithium or desipramine alters discharge frequency and norepinephrine responsiveness of cerebellar Purkinje cells.

Abstract

Cerebellar Purkinje cells were studied by electrophysiological techniques in rats treated chronically with either desipramine (DMI) or lithium chloride given intragastrically. A striking decrement occurred in discharge frequencies of simple spikes and climbing fiber bursts in both groups of animals, similar to the depression produced by iontophoresis of these agents. Chronic treatment with DMI markedly de- METHODSA total of 25 adult albino rats were used, with five groups in the DMI study. The first group ("chronic DMI, high") received, by gavage, DMI-HCl at 50 mg/kg in 2 ml of tap water once daily for 3 days, and then 30 mg/kg per day thereafter for 7-11 days. The second group ("chronic DMI, low") received DMI at 30 mg/kg per day for 8-18 days. These two "chronic groups" were tested electrophysiologically 24-36 hr after the last dose, when cerebellar DMI is roughly one-half the level during treatment (unpublished data). The third group ("controls") received 2 ml of tap water by gavage daily for 6-10 days. The fourth group ("DMI withdrawal") received DMI daily for 10 days and then treatment was terminated for 5 days before testing. In the fifth group ("acute DMI") animals received only one dose of DMI (30 mg/kg) by gavage prior to anesthesia and testing. The intragastric route of administration was chosen to maintain fairly constant brain levels of DMI and to avoid the peritonitis and resultant disruption of drug absorption often associated with chronic intraperitoneal injection.Four groups of animals were studied for Li effects. In the first group ("chronic Li"), LiCl at 60-75 mg/kg was administered once per day in 2 ml of water, by gavage for 9-12 days supplemented by ad lib intake of 10-15 mg/kg per day in the drinking water which also contained 0.9% NaCl. This group was tested electrophysiologically 2-12 hr after the last dose of LiCl, when serum Li levels were equal to those during treatment (unpublished data). A control group of rats received NaCl at 75 mg/kg per day by gavage as well as 0.9% NaCl in the drinking water. A third group ("Li withdrawal") received LiCI

Neurobiological basis of depression: an update

“…There appears to be a close correlation between electrophysiology and antidepressant-induced desensitization of the postsynaptic b-adrenoceptor system, as evidenced by a significant reduction in the sensitivity of cortical pyramidal and cerebellar Purkinje cells to noradrenaline after chronic treatment with tricyclic antidepressants and MAO inhibitors [22]. Chronic administration of antidepressants leads to an increase in the inhibitory response of forebrain neurons to microiontophoretically applied serotonin and/or dopamine [23].…”

Epinephrine, the neglected catecholamine

“…To what extent the above findings concerning increased organ output in the periphery are applicable to the CNS is not known. There have been several demonstrations of reduced sensitivity to NE in central neurons following chronic antidepressant treatment (Huang 1979a;Olpe & Schellenberg 1980;Siggins & Schultz 1979). In each of these experiments reduced sensitivity was inferred from a decreased NE-mediated inhibition of the firing rate of neurons postsynaptic to noradrenergic nerve endings.…”