Receptor characteristics and recovery of function following kainic acid lesions and fetal transplants of the striatum. I. Cholinergic systems.

ABSTRACT

The relationship between striatal muscarinic cholinergic receptor development and locomotor activity/T-maze alternation behavior in adult female rats with kainic acid lesions (kal) and fetal transplants of the striatum (str) was examined. Kal led to a number of deficits under conditions of spontaneous locomotion, including (1) decreased stereotypical and increased horizontal movements during spontaneous overnight locomotion, (2) decreased spontaneous alternation on a T-maze, and (3) deficits on a sensorimotor neurological exam. Lesion-induced deficits following injection with cholinergic agonists (pilocarpine)/antagonists (scopolamine) included (1) hypoactivity on vertical activity and stereotypical activity following scopolamine injection, and (2) increased stereotypical activity and decreased horizontal activity following pilocarpine injection. Transplants differentially affected the different types of behavioral deficits. Transplants reversed some of the deficits under conditions of spontaneous locomotion, including the hyperactivity noted during the night period, but only partially reversed the sensorimotor neurological exam and had no effect on spontaneous alternations in the T-maze. The transplants did not reverse the lesion-induced deficits following scopolamine injection, but partially reversed the lesion-induced changes in locomotion following pilocarpine injection. The striatal transplants had reduced numbers of M1 but increased numbers of M2 muscarinic cholinergic receptors. Cholinergic receptor density correlated with scores on the sensorimotor functioning and alternation tasks, but not with the locomotor measures. Conversely, the cross-sectional area of the str correlated strongly with the transplant-induced recovery in the lesion group. These results suggest that the development of cholinergic receptor systems within the transplants proceeds abnormally, and that the abnormal development of the transplant may impact on the transplant's ability to remediate lesion-induced deficits.