Effects of clonidine in the locus coeruleus on prefrontal- and hippocampal-dependent measures of attention and memory in the rat

Abstract

The locus coeruleus (LC) is the source of norepinephrine (NE) in the prefrontal cortex (PFC) and hippocampus and may influence cognitive functions of these areas. Chronic effects of LC-NE lesions do not correspond consistently with acute effects of systemic or intracortical injections of adrenergic agents. These studies aim to manipulate LC activity pharmacologically and study acute effects on measures of attention and memory that depend on the PFC and hippocampus. Rats were trained to criterion for one of three tasks: visuospatial reaction time (VSRT), a measure of attention sensitive to PFC lesions, delayed matching trained with retractable levers (DM-RL), and delayed nonmatching trained in radial mazes (DNM-RM), measures of spatial working memory sensitive to PFC and hippocampal lesions, respectively. LC activity was manipulated with bilateral 0.5-microl injections of the alpha-2 agonist clonidine (0, 1.1, 4.5, and 18 nmol). Clonidine produced significant dose-dependent impairments of VSRT, affecting choice response time at the 18-nmol dose and choice accuracy at the 4.5- and 18-nmol doses. Clonidine had no effect on DMRL or DNM-RM at any of the doses tested. Reversible reduction of LC-NE activity by clonidine impaired measures of visuospatial attention sensitive to PFC lesions but were insufficient to affect PFC- or hippocampal-dependent measures of spatial working memory. These results are consistent with reports that LC-NE lesions produce chronic deficits in attention with little or no effect on measures of working memory.