Handedness in rats: Blockade of reaching behavior by unilateral 6-OHDA injections into substantia nigra and caudate nucleus

Abstract

Unilateral 6-hydroxydopamine (6-OHDA) injections into the nigrostriatal system of rats were used to interfere with a lateralized reaching-for-food habit, the so-called “handedness.” Experiment 1: Although injections of 6-OHDA into the substantia nigra (8 µg/4 µl) ipsilateral (n=7) to the preferred forelimb had no effect on the overlearned instrumental reaction, reaching was blocked 15 min after contralateral (n=12) injection of the neurotoxin and remained suppressed for the 8 days of testing. At the same time, retrieval of food with the nonpreferred forepaw significantly increased. Although the rats failed to reach into the feeder, behaviors like grasping, grooming, or holding food pellets were intact in the “neglected” forepaw. Nonspecific effects such as changes in activity level or motivation could be ruled out by the ipsilateral-contralateral test paradigm used. The early behavioral asymmetries (blockade of handedness, flexion of the forelimb, and ipsilateral turning) are interpreted as due to interference of 6-OHDA with membrane structures of dopaminergic neurons. Experiment 2: Injections of 6-OHDA into the caudate nucleus contralateral (30 µg/5 µl, n=9) to the performing forelimb initially blocked handedness similarly as in Experiment 1. However, in contrast to nigral injections, reaching recovered within 6 days. Experiment 3: One month after a unilateral 6-OHDA lesion of substantia nigra, naive rats (n=7) acquired the reaching-for-food habit with the paw ipsilateral to the lesion. It is concluded that the blockade of handedness produced by unilateral 6-OHDA lesions of substantia nigra is not due to paralysis of the forelimb but to faulty integration of the contralateral somatosensory signals with contralateral motor patterns.