INTRASTRIATAL 3-NITROPROPIONIC ACID - A BEHAVIORAL-ASSESSMENT

SYSTEMIC injections of 3-nitropropionic acid (3-NP) in Sprague-Dawley rats have led to (1) hypoactivity that resembles juvenile onset and ad vanced Huntington's disease (HD), and (2) impairment in contextual ret ention of passive avoidance. Since it has been established that 3-NP e xerts its primary effects in the striatum, we selected intrastriatal i njections to more thoroughly understand the direct behavioral effects of 3-NP. Each 14-week old rat received bilateral intrastriatal injecti ons of one of the following: 500 and 750 nmol of 3-NP or vehicle (0.9% saline). At seven days following surgery, the animals were tested for spontaneous locomotor behavior and passive avoidance behavior. Result s revealed deficits in both locomotor activity and passive avoidance l earning. The animals injected with 500 and 750 nmol of 3-NP were signi ficantly hypoactive compared with control animals. Similarly, the 2 gr oups of animals were severely impaired in the retention of passive avo idance compared with control. The 3 groups, however, did not differ in their acquisition of this learning task. Macroscopic analyses of brai ns of these animal revealed that 500 and 750 nmol of 3-NP caused sever e loss of neuronal cell bodies and marked glial infiltration in the me dial aspect of the striatum. Larger lesions showed a necrotic cavity a t the injection site. In comparison with systemic administration of 3- NP, intrastriatal injections resulted in more profound hypoactivity, g reater loss of passive avoidance retention, and more severe striatal d amage. The present study supports the behavioral findings of systemic 3-NP administration and suggests that the behavioral symptoms in this unique animal model of HD are due to striatal damage following 3-NP.