McGaughy JA (2006) The effects of a norepinephrine reuptake blocker, atomoxotine, on an attentional set shifting impairment caused by prefrontal lesions. Neuroscience 2006 Abstracts 749.17. Society for Neuroscience, Atlanta, GA.
Summary: There is substantial evidence to support the role of norepineprhine (NE) in selective attention. The NE system is hypothesized to maintain task-related attentional focus and allow shifts of attention (Aston-Jones and Cohen, 2005). These unique attentional functions correlate with changes in the firing patterns in locus coeruleus. Previous work in our lab has shown that NE lesions of the medial prefrontal cortex produces robust impairments in the ability of rats to perform an attentional set-shift, though acquisition of the attentional set and reinforcement reversal learning were spared. The current study assesses the effectiveness of atomoxotine, a NE reuptake blocker, in remediating these deficits. This drug is currently used in the treatment of attention deficit disorder and may restore balance to the noradrenergic system of the frontal cortex in these patients. Male, Long-Evans rats received lesions of the medial wall of the prefrontal cortex using dopamine beta-hydroxylase saporin (DBH-SAP) to produce selective noradrenergic deafferentation. The performance of DBH-SAP rats was compared to sham-lesioned (SHAM) rats in a test of attentional set-shifting after intraperitoneal injections of atomoxotine (0.0, 0.1,0.3, 0.9 mg/kg) 15 minutes prior to the test of attentional set-shifting. During the attentional set shifting task (Birrell and Brown 1999), rats were exposed to complex stimuli (texturized, scented pots filled with digging media). Initially rats were reinforced for focusing attention on one stimulus dimension, e.g. scent, during the tests of complex discriminations and reinforcement reversals. In tests of attentional set-shifting, subjects were required to inhibit attention to the previously reinforced dimension e.g. scent and learn that a new dimension e.g. texture predicted reinforcement.These results confirm that NE deafferentation of prefrontal cortex impairs the ability of rats to shift attention from the initially reinforced dimension to another dimension, e.g. when texture not odor now predicts reinforcement. Low doses of atomoxotine ameliorate the set-shifting impairments of DBH-SAP rats but hindered the performance of SHAM rats. These data suggest that shifts of attentional set require an optimal level of release of NE in the frontal cortex with both high and low levels of NE causing impairments in these abilities.
Related Products: Anti-DBH-SAP (Cat. #IT-03)