Effects of Melatonin on the Behavioral Indices and Structural Characteristics of Cerebral and Spinal Neurons of Rats with Experimental Hemiparkinsonism

In adult Wistar rats, a model of experimental hemiparkinsonism (EHP) was induced by stereotaxic microinjection of 8.0 μg 6-hydroxydopamine (6-HODA) into the left forebrain lateral ascending bundle. In such animals, we studied behavioral indices in the open field and elevated plus maze tests and also structural changes in the cerebral substantia nigra and spinal L5 ventral horn neurons. Six groups of animals were formed (in each group, n = 8): intact rats (I), animals that obtained microinjections of saline into the above lateral bundle (sham-injected, ShI), two groups with weak and intense motor EHP manifestations (frequency of circulatory movements in the apomorphine test less than one and six and more per 1 min, groups HP_<1 and HP_≥6, respectively), and two groups of rats with weak and intense EHP manifestations, which obtained daily i.p. injections of 10 mg/kg melatonin during 18 days (groups HP_<1+M and HP_≥6+M). In the open-field test, we observed in groups HP_<1 and HP_≥6 significant suppression of horizontal motor activity (very intense in the latter of the above-mentioned groups) and also significant weakening of vertical activity (number of rearings). Changes in the number of defecation acts were less expressed. In the elevated plus maze, manifestations of a significantly increased anxiety level were observed in rats of the above two groups. In the substantia nigra of animals with EHP, a considerable part of the neurons demonstrated clear signs of negative structural modifications; the number of neurons with the normal structure was considerably smaller than in the control. Analogous negative morphological changes were found in the lumbar segment of the spinal cord. Course injections of melatonin into rats with EHP noticeable weakened negative shifts in both open-field behavioral indices and level of anxiety (according to estimates in the elevated plus maze). Under the action of melatonin, morphological characteristics of neurons and gliocytes in the substantia nigra and spinal cord of rats with EHP demonstrated appreciable normalization. The mechanisms underlying functionaland structural disorders in the CNS of animals after central microinjections of the 6-HODA neurotoxin and also neuroprotective effects of melatonin, which provide weakening of such disorders, are discussed.

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