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Stimulation of D1- or D2-receptors in drug-naive rats with different degrees of unilateral nigro-striatal dopamine lesions

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Abstract

We had previously found that in animals with moderate nigro-striatal dopamine (DA) lesions (i.e. 45–65% residual neostriatal DA) the mixed D1/D2-agonist apomorphine induced ipsiversive rather than the usual contraversive turning found after more radical DA lesions. Since this result promised to provide a behavioral animal model for pre-clinical Parkinson's disease, we hoped to delineate the responsible receptor by challenging with selective D1- and D2-agonists. Thus, in the present study, the behavioral effects of the D1-agonist SKF38393 (5.0 mg/kg) and the D2-agonist LY171555 (0.5 mg/kg) were tested in drug-naive rats with unilateral 6-hydroxydopamine lesions of the nigro-striatal DA system. This analysis was performed dependent on the degree of the lesion, classified post-mortem with respect to the level of residual DA in the neostriatum: <20%, 20–45%, 45–65%, and >65% (as percentage of the intact hemisphere). The measures of turning, thigmotactic scanning and locomotion did not yield differences between animals treated with the D1-agonist and vehicle-treated rats. For example, animals with severe lesions (residual DA <20%) showed ipsiversive asymmetries in turning and scanning, which were similar after vehicle or the D1-agonist, both with respect to degree and time-course. However, the analysis of grooming behavior, which was performed in a subset of animals with moderate lesions yielded differences between vehicle and the D1-agonist, since the duration of grooming was increased after SKF38393. In contrast to the D1-agonist, behavioral effects after the D2-agonist LY17155 were evident in all behavioral measures. The general response to this agonist could be characterized by a rapid decrease of behavioral activity including turning, scanning, locomotion and grooming. Although we failed to find significant behavioral asymmetries with either agonist, a micro-analysis showed evidence for selective effects after the D2-agonist, since a contraversive asymmetry in turning (and scanning) became apparent between 45 and 60 min after injection in animals with severe lesions (residual DA of about 10% or less), and since there was a weak ipsiversive turning asymmetry in animals with residual DA levels of 45–65%. Such asymmetries were not observed after vehicle or the D1-agonist. The possible physiological mechanisms of these effects, i.e. DA receptor mechanisms and DA availability, are discussed in the context of results from previous experiments using lesioned or intact animals.

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Authors and Affiliations

  1. Institute of Physiological Psychology I, and Biologisch-Medizinisches Forschungszentrum, Heinrich-Heine University of Düsseldorf, Universitätsstr 1, 40225, Düsseldorf, Germany

    J. Fornaguera, J. P. Huston & R. K. W. Schwarting

  2. Research and Development Service, VA Medical Center, 13210, Syracuse, NY, USA

    R. J. Carey

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  1. J. Fornaguera
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  3. R. K. W. Schwarting
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  4. R. J. Carey
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Fornaguera, J., Huston, J.P., Schwarting, R.K.W. et al. Stimulation of D1- or D2-receptors in drug-naive rats with different degrees of unilateral nigro-striatal dopamine lesions. Psychopharmacology 119, 145–154 (1995). https://doi.org/10.1007/BF02246155

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  • DOI: https://doi.org/10.1007/BF02246155

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