Intravenous Ethanol Administration and Operant Self-Administration Alter Extracellular Norepinephrine Concentration in the Mesocorticolimbic Systems of Male Long Evans Rats.

Abstract

Norepinephrine has been suggested to regulate ethanol (EtOH)-related behaviors, but little is known about the effects of EtOH on norepinephrine release in mesocortical and mesolimbic brain areas that are targets of EtOH actions. We used in vivo microdialysis to examine the effects of EtOH on extracellular norepinephrine concentrations in mesocorticolimbic brain regions of male Long Evans rats. We determined the effects of intravenous infusion of saline or EtOH in the medial prefrontal cortex (mPFC) and the basal forebrain. We also measured dialysate norepinephrine concentrations during operant self-administration of EtOH in the mPFC. Intravenous infusion (1 or 0.25ml/min) of 1.0g/kg EtOH stimulated an increase in dialysate norepinephrine in mPFC and in basal forebrain. In the basal forebrain, an infusion of 0.5g/kg EtOH did not stimulate dialysate norepinephrine concentrations. In both regions, saline infusions did not increase dialysate norepinephrine concentrations. In the behavioral experiment, 1week of experience with operant self-administration of sweetened EtOH resulted in an apparent reduction in basal dialysate norepinephrine concentrations in the mPFC relative to the sucrose control. Dialysate norepinephrine increased during the transfer from home cage to the operant chamber in all groups. We conclude that acute EtOH stimulates both the locus coeruleus (which projects to the mPFC) and the nucleus tractus solitarius (which projects to the basal forebrain) noradrenergic neurons. Additionally, limited EtOH self-administration experience alters dialysate norepinephrine in the mPFC in a manner consistent with a decrease in tonic norepinephrine release. Further studies are necessary to elucidate the mechanisms by which EtOH exerts these variable effects.