Effects of Acute Intracerebroventricular Microinfusions of Bupropion on Background Spike Activity of Locus Coeruleus Neurons in Rats

Abstract

Considering that noradrenergic (NAE) neurons of the locus coeruleus (LC) play significant roles in the formation of biological rhythms, pain, addictions, and mood disorders, we tested the effects of acute intracerebroventricular microinfusions of bupropion, an inhibitor of NA reuptake used in clinics as an antidepressant, on background spike activity on LC neurons in chloral hydrate anesthetized rats. Ten microliters of the solutions containing 0.001, 0.01, 0.1, 1.0, or 10.0 mu mol bupropion were infused during 3 min; spike activity of single LC neurons identified according to the known characteristics was recorded extracellularly by glass microelectrodes. Microinfusions of 0.01 to 10.0 mu mol bupropion suppressed background spiking of the above neurons in a dose-dependent manner. The normalized mean intensities and durations of inhibition were 17.3, 19.4, 26.3, and 41.1% and 1.4, 7.1, 12.4, and 18.3 min, respectively. The smallest dose (0.001 mu mol) was ineffective. It is assumed that bupropion increases the NA level in proximity to NAE LC neurons. The actions of bupropion on other cerebral neuromodulatory systems need further examination. Inhibition of LC neuronal activity by bupropion can help to explain some acute, chronic, and side effects of this agent used in clinics for correction of mood disorders.