THE EFFECT OF MELATONIN IN PROTECTING AGAINST THE BEHAVIORAL CONSEQUENCES OF CHRONIC HYPOPERFUSION IN MIDDLE-AGED FEMALE RATS

Mild cognitive impairment (MCI) is a growing disorder among the elderly and can often go unnoticed for a significant portion of time. MCI is often preceded by vascular dysfunction and has the potential to cause irreversible damage to one’s cognitive ability. The neurocognitive consequences of MCI can be imitated through the use of the 2-vessel occlusion (2VO) procedure in rats, which limits cerebral blood flow (CBF) through bilateral arterial ligation. Therefore, the current study investigated whether chronic melatonin would attenuate 2VO induced behavioral deficits in middle-aged female rats. Thirty 9- to 11-month-old female Sprague-Dawley rats were randomly assigned to one of three groups: sham, 2VO and 2VO animals that received melatonin. Melatonin was administered 2 weeks prior to the 2VO surgery as a pretreatment. The 2VO rats showed a significant increase in locomotor activity which was attenuated by melatonin treatment. 2VO rats also exhibited a significant increase in exploratory behavior that was also reduced by melatonin treatment. Melatonin treated rats also exhibited higher spontaneous alternation compared to 2VO and sham rats. Neither 2VO nor melatonin exhibited altered performance on visual and object recognition tasks. Similarly, no spatial learning deficits were observed using the Morris Water Maze task. These findings indicate that melatonin pretreatment is capable of reversing ischemia-induced hyperactivity suggesting that it had a neuroprotective role. 2VO did not cause significant deficits in learning and memory however middle-aged rats may have subtle age-related impairments in these tasks hence making it more difficult to detect a 2VO induced deficit.