FUNCTIONAL-CHANGES INDUCED BY NEONATAL CEREBRAL 6-HYDROXYDOPAMINE TREATMENT - EFFECTS OF DOSE LEVELS ON BEHAVIORAL PARAMETERS

Male Sprague-Dawley rats were treated neonatally with either of three different doses of 6-hydroxydopamine (6-OHDA): 50 mu g i.c., 75 mu g i .c., or 2 x 100 mu g i.c.v., 30 min after a subcutaneous injection of desipramine (DMI, 25 mg/kg), in order to obtain selective lesions of m esencephalic dopamine (DA) neurons to different extents. From juvenile ages onwards, rats in each dose condition were tested for spontaneous motor activity and exploration in an openfield/holeboard setting meas uring ambulation, rearing and head-dips. Between 77 and 78 days, the a nimals were tested in a modified, enclosed radial arm maze, followed 1 week later by tests in the circular swim maze. Finally, motor activit y was tested in automated activity test chambers. In the openfield/hol eboard setting, hyperactivity was seen for both rearing and ambulation in rats administered 50 mu g 6-OHDA, whereas the 75 mu g and 2 x 100 mu g groups showed hyperactivity for ambulation, but hypoactivity for rearing and head-dips. All three dose groups demonstrated a retardatio n of learning in the radial arm maze. The 75 and 2 x 100 pg groups, bu t not the 50 mu g group, showed impairments of acquisition in the swim maze. In the activity test chambers locomotion and rearing behavior v aried as a function of 6-OHDA dose, being negatively and positively, r espectively, related to DA concentration in striatum. These results sh ow that the extent of the neonatal DA lesion determines both changes i n motor- and exploratory activity as well as the occurrence and severi ty of acquisition impairment in spatial learning tasks.