Cerebellar norepinephrine depletion and impaired acquisition of specific locomotor tasks in rats

Previous work in our laboratory has shown that norepinephrine (NE)-depleted rats manifested impaired acquisition of a locomotor task as measured in a new rod runway paradigm. This paradigm involved the initial training of water-deprived rats on an equally spaced regular rod arrangement (REG), and subsequent testing, after intracisternal 6-hydroxydopamine (6-OHDA; 3 X 25 micrograms/microliter free base) infusion, on a more difficult irregular rod arrangement (IRR). These NE-depleted animals manifested impaired acquisition of the task as measured by running times (RT, 25 trials/day) over a 4 day post-infusion test period (IRR). In this present study, this same REG/IRR paradigm was employed in combination with a localized 6-OHDA lesion of the coeruleo-cerebellar pathway. A bilateral infusion of 6-OHDA (8 micrograms/2 microliters) induced cerebellar noradrenergic deafferentation (26% of controls) and produced a significant impairment of 4 day post-infusion RT. Thus, the coeruleo-cerebellar-lesioned rats demonstrated acquisitional impairment when tested on the new locomotor task (IRR). Moreover, the degree of impaired acquisitional, but not initial post-infusion motor performance, was found to correlate directly with the degree of cerebellar noradrenergic deafferentation. Furthermore, these rats showed no arousal, motivational or general cognitive learning deficits since no significant differences were observed in runway intertrial interval times, open field behavior, or in reversal of a T-maze position habit. Thus, cerebellar NE appears to be strongly associated with the adaptive ability to coordinate and choreograph the movements necessary to perform in this locomotor task.