Caffeine prevents neurodegeneration and behavioral alterations in a mice model of agitated depression.

Abstract

Longitudinal and some experimental studies have showed the potential of caffeine to counteract some depressive

behaviors and synaptic dysfunctions. In this study, we investigated the potential of caffeine in preventing be- havioral outcomes, neurodegeneration and synaptic proteins alterations in a mice model of agitated depression

by bilateral olfactory bulbectomy (OB). For this purpose, bulbectomized mice received caffeine (0.3 g/L and 1.0 g/L, drinking water), during the active cycle, for seven weeks (two before the surgery and throughout five weeks after OB). Caffeine prevented OBinduced hyperactivity and recognition memory impairment and rescue

self care and motivational behavior. In the frontal cortex, bulbectomized mice presented increase in the ade- nosine A1 receptors (A1R) and GFAP, while adenosine A2A receptors (A2AR) increased in the hippocampus and

striatum and SNAP-25 was decreased in frontal cortex and striatum. Caffeine increased A1R in the striatum of bulbectomized mice and in SHAM-water group caffeine increased A2AR in the striatum and decreased SNAP-25

in the frontal cortex. Astrogliosis observed in the polymorphic layer of the dentate gyrus of OB mice was pre- vented by caffeine as well as the neurodegeneration in the striatum and piriform cortex. Based on these beha- vioral and neurochemical evidences, caffeine confirms its efficacy in preventing neurodegeneration associated

with memory impairment and may be considered as a promising therapeutic tool in the prophylaxis and/or treatment of depression.