Effect of Chronic Melatonin Pretreatment on Neural and Behavioral Consequences of Global Ischemia in Male Gerbils

Melatonin has been shown to be an effective neuroprotectant against the neural and behavioral consequences of global ischemia in previous research; however, there is little information as to how melatonin may be used as a chronic prophylactic treatment against ischemic injury in male gerbils The current study sought to determine if chronic melatonin treatment (via a time-released subcutaneous pellet) initiated 2 weeks prior to ischemia attenuates ischemia-induced CA1 cell loss, locomotor hyperactivity, and changes in spontaneous alternation. Gerbils were divided into either a sham, placebo-treated, or melatonin-treated ischemic groups. Ischemic groups were subjected to 5-minute bilateral occlusion of the carotid arteries. Global ischemia produced significant neuronal loss in the CA1 and resulted in a significant increase in locomotor hyperactivity. Exploratory and anxiety-like behavior were not affected by global ischemia. Spontaneous alternation behavior was also unaltered. Chronic melatonin treatment did not afford neuronal protection or decrease locomotor hyperactivity. Analysis of the global ischemic injury revealed a high mortality rate and variable injury in the current sample. This is thought to be due to increasing anatomical variability in the gerbil global ischemia model. The low sample size and inconsistent ischemic injury suggest that the insignificant results of the current study are not definitive of chronic melatonin’s pretreatment potential. Future research using larger sample sizes to account for the increasing variability in the gerbil model is encouraged to clarify the chronic prophylactic potential of melatonin.