Molly C. McCloskey, Tyler J. Young, Shawn M. Anderson
BIOS 88 (1), 29-38, (1 March 2017) https://doi.org/10.1893/BIOS-D-15-00013.1
In today's society, numerous people suffer from anxiety and depression, so it is important to develop effective treatments for these disorders. However, there is limited knowledge of the mechanisms underlying them. Previous studies show that increased acetylcholine (ACh) levels in the hippocampus positively correlate with increased depression. Acetylcholinesterase (AChE) is the principle degradative enzyme of ACh in the brain and limits the concentrations of ACh in the neuronal synapse. Furthermore, chronic administration of the antidepressant fluoxetine resulted in reduced anxiety- and depression-like behavior in mice. Therefore, we hypothesized that mice receiving chronic administration of fluoxetine would show reduced anxiety- and depression-like behaviors, which would negatively correlate with higher levels of AChE in the hippocampus. These hypotheses were tested using behavioral and molecular assays. Adult male Swiss-Webster mice received daily i.p. injections of either 20 mg/kg fluoxetine or vehicle. After two weeks of treatment, relative levels of anxiety- and depression-like behavior were determined. The novelty-induced hypophagia (NIH) and open field tests determined anxiolytic-like efficacy of fluoxetine, and the tail suspension and forced swim tasks evaluated depression-like behavior. Upon completion of behavioral testing, the brains were extracted, core samples were taken from the striatum, dorsal hippocampus, and basolateral amygdala, and the AChE levels were measured. Fluoxetine-treated mice showed significantly reduced latencies to ingest a palatable solution in a novel environment, suggestive of reduced anxiety-like behavior (p < 0.05). Significant positive correlations were observed between AChE levels in the striatum and time spent in center in the open field test (p < 0.05), suggesting decreased cholinergic tone correlates to reduced anxiety, but the correlations were not consistent across behavioral assays.