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The Journal of Neuroscience, February 11, 2004, 24(6):1385-1392; doi:10.1523/JNEUROSCI.4664-03.2004
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Behavioral/Systems/Cognitive
The Basolateral Amygdala Interacts with the Medial Prefrontal Cortex in Regulating Glucocorticoid Effects on Working Memory Impairment
Benno Roozendaal,
Jayme R. McReynolds, and
James L. McGaugh
Center for the Neurobiology of Learning and Memory, Department of Neurobiology and Behavior, University of California, Irvine, California 92697-3800
Previous findings indicate that the basolateral complex of the amygdala (BLA) interacts with other brain regions in regulating stress hormone effects on memory functions. Lesions of the BLA or infusions of a  -adrenoceptor antagonist into the BLA block glucocorticoid effects on both memory consolidation and retrieval when administered either systemically or directly into the hippocampus. The present experiments examined BLA and -adrenoceptor involvement in regulating glucocorticoid effects on spatial working memory, a task that depends on the medial prefrontal cortex (mPFC). Male Sprague Dawley rats with bilateral sham- or NMDA-induced lesions of the BLA received either corticosterone (1.0 or 3.0 mg/kg, i.p.) systemically or the specific glucocorticoid receptor agonist 11,17-dihydroxy-6,21-dimethyl-17 -pregna-4,6-trien-20yn-3-one (RU 28362; 3.0 or 10.0 ng in 0.5 µl) into the mPFC shortly before testing on a delayed alternation task in a T-maze. Both glucocorticoid treatments induced comparable impairments in working memory performance in sham-lesioned controls. Although lesions of the BLA alone did not affect working memory, BLA lesions blocked the impairment induced by either corticosterone or RU 28362. Likewise, systemic injections of the centrally acting -adrenoceptor antagonist propranolol (2.0 mg/kg, i.p.) given before testing prevented corticosterone-induced working memory impairment. These findings indicate that BLA activity is essential for enabling glucocorticoid effects in the mPFC on working memory and suggest that stress hormone-induced modulation of working memory involves noradrenergic activation.
Key words: -adrenoceptor; corticosterone; delayed alternation task; glucocorticoid receptor; norepinephrine; propranolol; RU 28362; stress hormone
Received June 12, 2003;
revised November 20, 2003;
accepted December 8, 2003.
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