Elevated body swing test: a new behavioral parameter for rats with 6- hydroxydopamine-induced hemiparkinsonism

Abstract

Parkinson's disease is characterized by a depletion of dopamine (DA) neurons in the nigrostriatal pathway. Stereotaxic injections of 6- hydroxydopamine (6-OHDA), a selective neurotoxin, into either the medial forebrain bundle or the substantia nigra result in a massive DA denervation of the nigrostriatal pathway. Following unilateral nigrostriatal DA depletion, hemiparkinsonian animals develop a stereotypical rotational behavior when challenged with DA agonists such as apomorphine. The drug-induced rotational behavior has been widely used as the behavioral index of hemiparkinsonian animals, but it has some limitations. Although asymmetries in the rotational behavior may indicate an imbalance of DA contents and release capacity in the bilateral nigrostriatal pathway, the behavior is a pharmacological reaction. Accordingly, the drug-induced rotation test is subject to sensitization effects. The present study proposes the elevated body swing test (EBST) as a measure of asymmetrical motor behavior of hemiparkinsonian animals in a drug-free state. The EBST simply involves elevating the animal by handling its tail and recording the frequency and direction of the swing behavior. Unilateral nigral 6-OHDA-lesioned rats exhibited significant biased swing activity with the direction contralateral to the lesioned side, corresponding to the direction of apomorphine-induced rotations. A 30 sec EBST was noted as the peak time for biased swing activity. At 7 d postlesion (the start of testing), and every week thereafter for a period of 2 months, a fairly stable biased swing activity level was observed. At 1 and 2 months postlesion, the same animals were also challenged with apomorphine.