Motor behavioural changes after intracerebroventricular injection of 6-hydroxydopamine in the rat: an animal model of Parkinson's disease

Abstract

At the beginning of the 1970s, different studies reported behavioural disturbances after the intracerebroventricular (icv) administration of 6-hydroxydopamine (6-OHDA) in the rat. Despite the fact that this neurotoxic agent degenerates brain dopaminergic (DA-) cells, its potential utility to produce a rat model of Parkinson's disease (PD) was never systematically studied because the aphagia and adipsia were often observed. In the present study, a procedure that induces a marked DA-cell degeneration that bypasses these and other undesirable complications of icv injection of 6-OHDA is reported. Lesioned animals (50–500 μg of 6-OHDA) showed a persistent motor syndrome composed of hypokinesia, purposeless chewing and catalepsy. The intensity of motor signs was dose-dependent, and recovered partially after administration of DA-receptor agonists, exposure to sensorial stimuli and stress, three procedures that reduce motor dysfunctions in Parkinson's disease (PD). Lesioned animals showed bilateral and symmetrical midbrain DA-cell degeneration with the highest cell-loss in A9 group (substantia nigra), followed by A8 (retrorubral field) and A10 (ventral tegmental area) groups. The similarity between the behavioural syndrome and the topographical profile of cell-loss after icv injection of 6-OHDA in rats and the clinical and neuropathological features of PD indicates that this may be a convenient animal model of PD particularly useful for checking in rats the possible efficacy of new anti-parkinsonian drugs on specific parameters of motor dysfunctions.