Methods

At 3 days after birth rat pups are pretreated with desi-pramine HCl (20mg/kg IP), 1h before bilateral ICV administration of 6-hydroxydopamine (6-OHDA; 67 mg, base, on each side) or saline-ascorbic acid (0.1%) vehicle. To administer the latter substances, rat pups are individually immersed in ice (^60 sec) to produce cold-anesthesia. Pups are then placed on a flat surface under a bright light. In this manner, the sagittal and transverse sinuses overlying the cranium, as well as bregma and lambda, can be seen through the transparent intact dermis. A 26-gauge needle, attached to a microliter syringe, is positioned 1.5 mm anterior to lambda and 2 mm lateral to the sagittal plane. The needle, equipped with a polyethylene sleeve up to 2 mm from the tip, is then lowered to the stop position (i.e., sleeve), with the needle in the lateral ventricle. After injection of 5 ml of 6-OHDA or vehicle, the needle is left in place for at least 30 sec. Immediately afterward, an injection is made in the same manner into the other lateral ventricle. Pups are warmed to promote recovery, and each pup is then returned to the litter. In adulthood, litters treated with 6-OHDA are generally ^5% smaller than controls -although this can be minimized if desired by exchanging dams (Brus et al., 1994). When these rats are used as a model of PD, there are no additional treatments during development or before the time of the PD study.

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