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

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Abstract

6-Hydroxydopamine (6-OHDA; 100 µg in 5 µl) 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-hydroxyin-doleacetic 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. Changes in NA and 5-HT levels were also found in telencephalic and mesencephalic regions. The 6-OHDA lesion led to a lasting handling-related hyper-reactivity and, following stimulation with direct or indirect DA agonists, to rotational behaviour with a pattern similar to that observed in rats unilaterally lesioned at adult stage with 6-OHDA.

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Authors and Affiliations

  1. Department of Neuroscience, Karolinska Institute, Stockholm, Sweden

    Johan Luthman

  2. Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden

    Mario Herrera-Marschitz

  3. Department of Neuropharmacology, CNS Preclinical R&D, Astra Arcus AB, Södertälje, Sweden

    Johan Luthman & Eva Lindqvist

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Luthman, J., Herrera-Marschitz, M. & Lindqvist, E. Unilateral neonatal intracerebroventricular 6-hydroxydopamine administration in rats: I. Effects on spontaneous and drug-induced rotational behaviour and on postmortem monoamine levels. Psychopharmacology 116, 443–450 (1994). https://doi.org/10.1007/BF02247476

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