Unilateral neonatal intracerebroventricular 6-hydroxydopamine administration in rats: I. Effects on spontaneous and drug-induced rotational behaviour and on postmortem monoamine levels

Abstract

6-Hydroxydopamine (6-OHDA; 100 micrograms in 5 microliters) was injected into the right ventricle (intracerebroventricular, ICV) of 3-day old Sprague-Dawley rats in an attempt to produce a unilateral neonatal dopamine (DA) lesion. At adult stage, the rats were studied for spontaneous, handling- and drug-induced rotational behaviour. The 6-OHDA-treated rats showed hyperreactivity at handling, in the animal facility and in the experimental sets. This behaviour was not observed in vehicle-treated rats, and it did not decrease through the successive experiments. Apomorphine (0.05-1 mg/kg, SC) and caffeine (20 mg/kg SC) produced contralateral rotation in neonatal 6-OHDA, but not in vehicle-injected rats. d-Amphetamine (0.2-2 mg/kg, SC) produced strong, dose-dependent, ipsilateral rotation, while the serotonin (5-HT) releasing agent, p-chloroamphetamine (2 mg/kg, SC) produced a short-lasting and weak ipsilateral rotation in the 6-OHDA-treated rats. On the 6-OHDA-injected side, DA and metabolites levels were reduced by > 70-90% in the striatum, the nucleus accumbens and the tuberculum olfactorium, while in the mesencephalon a 50% decrease was found. On the contralateral side, restricted decreases in DA and metabolites were observed. Noradrenaline (NA) levels were decreased bilaterally in the forebrain. In contrast, 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels were increased in the ipsilateral striatum (> 180%), and tuberculum olfactorium (> 120%). Thus, neonatal unilateral ICV 6-OHDA administration produced a significant unilateral decrease in tissue levels of DA and metabolites, which was most marked in the striatum.(ABSTRACT TRUNCATED AT 250 WORDS)