The effect of beta-adrenoreceptor blockade during chronic exercise on contextual fear conditioning and mRNA for BDNF
Van Hoomissen, Jacqueline Dierickx
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Chronic exercise increases brain-derived neurotrophic factor (BDNF) messenger RNA (mRNA) in the brain and has been hypothesized as a biologically plausible explanation for the beneficial effects of exercise on brain function. The behavioral significance of the elevated levels of BDNF, however, is unknown. In addition, few studies have investigated the mechanism by which exercise leads to an increase in BDNF mRNA. Moreover, the regional specificity of the increase has not been examined. In the first experiment, we examined the regional specificity of the increase in BDNF mRNA after exercise and compared the effects of activity wheel running and antidepressant pharmacotherapy in the olfactory bulbectomy animal model of depression. Exercise or imipramine treatment alone increased BDNF mRNA in the hippocampal formation (HF) and ventral tegmental area/substania nigra regions of the brain. Exercise and imipramine combined did not potentiate BDNF mRNA expression above the levels observed with either treatment alone. These results indicate that the effect of exercise and antidepressant pharmacotherapy on BDNF mRNA is not limited to the HF and that the previously demonstrated potentiation of BDNF mRNA by exercise and pharmacotherapy may be time limited. In the second experiment, we explored the mechanism for, and the behavioral significance of, the increase in BDNF mRNA after exercise by examining the effect of activity wheel running and â-adrenoreceptor antagonism on contextual fear conditioning (CFC). Freezing behavior during the testing session of the CFC protocol was elevated above control levels in the activity wheel running animals that were treated with saline. This effect was attenuated by chronic treatment with propranolol. BDNF mRNA levels in the HF were elevated above home cage levels in all groups that underwent CFC, but were not different among the groups. These results suggest that aversively motivated learning is enhanced by chronic exercise and that CFC alters gene expression for BDNF in brain regions important in learning and memory.