Functional changes induced by neonatal cerebral 6-hydroxydopamine treatment: effects of dose levels on behavioral parameters.

ABSTRACT

Male Sprague-Dawley rats were treated neonatally with either of three different doses of 6-hydroxydopamine (6-OHDA) 50 micrograms i.c., 75 micrograms i.c., or 2 x 100 micrograms i.c.v., 30 min after a subcutaneous injection of desipramine (DMI, 25 mg/kg), in order to obtain selective lesions of mesencephalic 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 measuring ambulation, rearing and head-dips. Between 77 and 78 days, the animals were tested in a modified, enclosed radial arm maze, followed 1 week later by tests in the circular swim maze. Finally, motor activity was tested in automated activity test chambers. In the openfield/holeboard setting, hyperactivity was seen for both rearing and ambulation in rats administered 50 micrograms 6-OHDA, whereas the 75 micrograms and 2 x 100 micrograms groups showed hyperactivity for ambulation, but hypoactivity for rearing and head-dips. All three dose groups demonstrated a retardation of learning in the radial arm maze. The 75 and 2 x 100 micrograms groups, but not the 50 micrograms group, showed impairments of acquisition in the swim maze. In the activity test chambers locomotion and rearing behavior varied as a function of 6-OHDA dose, being negatively and positively, respectively, related to DA concentration in striatum. These results show that the extent of the neonatal DA lesion determines both changes in motor- and exploratory activity as well as the occurrence and severity of acquisition impairment in spatial learning tasks.