Behavioral quantification of striatal dopaminergic supersensitivity after bilateral 6-hydroxydopamine lesions in the mouse

Abstract

Quantitative studies using dopamine (DA) agonist-induced rotational behavior after denervation have found that the behavioral sensitivity is much greater than would be predicted on the basis of striatal DA receptor upregulation alone. The sensitivity to DA agonists after chronic treatment with neuroleptics, which elicits striatal receptor alterations equal to denervation, displays increases more consistent with alterations in striatal receptor density. Since the behavioral paradigms used to assess agonist supersensitivity after denervation are different than that for chronic neuroleptic treatment (rotational vs. stereotypic behavior), we measured the behavioral supersensitivity after bilateral denervation using stereotypic behavior. The increase in sensitivity to apomorphine after bilateral nigrostriatal 6-hydroxydopamine lesions was consistent with the increases measured previously with rotational behavior. These data suggest that the quantitative difference observed in behavioral supersensitivity resulting from the different preparations lies with the biological consequences of denervation rather than with the behavioral paradigm.