ergoline and Nerve-Degeneration

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

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Behavior, Animal; Dopamine; Ergolines; Locomotion; Male; Nerve Degeneration; Oxidopamine; Parkinson Disease; Quinpirole; Rats; Rats, Wistar; Receptors, Dopamine D1; Receptors, Dopamine D2; Substantia Nigra; Time Factors

The purpose of this study was to examine the effects of blockade (sulpiride) and activation (quinpirole) of dopaminergic D2 (DA2) receptors on brain lesions subsequent to excessive activation of glutamate (GLU) receptors. Striatal lesions were produced by direct injection of quinolinic acid, an endogenous GLU receptor agonist. Sulpiride (100 mg kg-1 i.p., 30 min before quinolinic acid injection and 1 h after) significantly (p < or = 0.05) reduced the volume of the lesion by around 20%. Quinpirole (1.25 mg kg-1 i.p., 30 min before quinolinic acid injection) had no effect. The protective action of DA2 receptor blockade strongly suggests that quinolinic acid-induced excitotoxicity may be partly modulated by DA2 receptors.

Topics: Animals; Corpus Striatum; Dopamine Agents; Dopamine Antagonists; Ergolines; Male; Necrosis; Nerve Degeneration; Quinolinic Acid; Quinpirole; Rats; Rats, Sprague-Dawley; Receptors, Dopamine; Receptors, Glutamate; Sulpiride