Relationships between indices of behavioral asymmetries and neurochemical changes following mesencephalic 6-hydroxydopamine injections

Behavioral and neurochemical changes were investigated in rats that had received one of 3 doses of 6-hydroxydopamine (6-OHDA), injected unilaterally into the ventral mesencephalon. The behavioral analysis comprised that of tight turns (diameter 55cm), and locomotor activity. 6-OHDA-injected animals were assigned to 3 different groups according to their degree of asymmetry in tight turns, both in spontaneous behavior and after the dopamine receptor agonist apomorphine (0.05 mg/kg). Thus, 6-OHDA-injected animals showed either (i) no spontaneous ipsiversive asymmetry (group 1), or (ii) an ipsiversive asymmetry, from which they did not recover during the three postoperative weeks of testing and which could not be reversed by apomorphine (group 2), or (iii) an even stronger ipsiversive asymmetry from which they did not recover but which could be reversed by apomorphine (group 3). The analysis of wide turns, which might reflect exploratory behavior of the environment, namely thigmotactic scanning, provided further information, as it indicated an asymmetry even in group 1; however, in contrast to the other groups a contraversive asymmetry was observed. Neurochemically, the three experimental groups were clearly different from each other with respect to the degree of neostriatal dopamine depletion, and the increase in dopamine metabolism in the damaged hemisphere as indicated by increased metabolite/transmitter ratios. The ipsiversive asymmetry in tight turns was negatively correlated with dopamine levels in the damaged neostriatum and positively correlated with the increase in metabolism. Furthermore, indications of changes in neostriatal serotonin activity were found. These results are discussed with respect to the necessity of differential measures of behavioral asymmetry, the role of dopaminergic mechanisms of 6-OHDA-induced deficits and mechanisms of recovery. The asymmetries in tight versus wide turns are suggested to reflect the preponderance of a motor deficit in the former case versus that of sensory neglect in the latter. Thus, the analysis of tight versus wide turns may provide distinctive and sensitive indices related to different functional deficits in animal models of hemiparkinsonism.