Caffeine Elicits Time Dependent Biphasic Response of Functional Recovery in Carassius auratus Hemilabyrinthectomy Lesion Model

Caffeine is one of the most popular psychostimulant drugs worldwide. Its effects are exerted through a variety of complex mechanisms, apparently primarily via interactions with adenosine A1 and A2A receptors. This drug has also been proven to elicit neuroprotective responses in a number of different brain disorders of the Central Nervous System (CNS), as well as provide enhancement of cognitive abilities. Moreover, a biphasic set of functional and structural neurological changes are often found in these receptors among diverse vertebrates. I investigated the effects of chronic caffeine exposure on functional recovery of the dorsal light reflex (DLR) in hemilabyrinthectomized common goldfish, Carassius auratus. In this lesion model the unilateral removal of vestibular organs results in the temporary loss of gravitational regulated postural control, which over time corrects itself by a vestibular compensation (VC) mechanism and can be quantified via the DLR. We compared the functional recovery over 24 post -surgery days in goldfish continuously held in a caffeine solution of 2.5mg/L (n=10), 5.0mg/L (n=10), 10.0mg/L (n=11) or a control 0.0mg/L (n=9). Compared to a sham surgery group (n=11), statistically significant changes in the DLR of all hemilabyrinthectomized goldfish was observed on day 1. The control group recovered over the study period by approaching but not entirely reaching sham surgery DLR. The 2.5mg/L and 5.0mg/L groups initiated postural recovery similar to the controls, but then regressed to a stronger DLR. Beginning on day 10 the caffeine groups deviated from the control and all three experimental caffeine groups were statistically different from the control group on days 15-24. Results suggest early caffeine exposure may be innocuous; however, chronic exposure inhibits the functional recovery process