BEHAVIORAL AND NEURAL BIOLOGY 61, 196--201 (1994) BRIEF REPORT Differential Recovery of Inhibitory Avoidance Learning by Striatal, Cortical, and Mesencephalic Fetal Grafts A. L. PICA, C. E. ORMSBY, AND F. BERMODEZ-RATTONI 1 Instituto de Fisiolog~a Celular, UNAM, Apdo. Postal 70-600, 04510 Mdxico, D.F., M~xico Four groups of male Wistar rats showing disrupted in- hibitory avoidance conditioning due to striatal lesions were studied. Three groups received striatal, cortical, or ventral mesencephalic brain grafts and the fourth group remained as a lesioned control. Sixty days postgraft the animals were retrained in an inhibitory avoidance task. The striatal-grafted animals were the only group that significantly improved in the ability to acquire the in- hibitory avoidance task. Acetylcholinesterase histochem- istry revealed positive patches of cells in the striatal grafts. Cortical grafts showed less reactivity, without patches. Immunocytochemical analyses for tyrosine hy- droxylase revealed positive cell reactivity in the mes- encephalic grafts and few positive fibers were detected in the border between the striatal grafts and the host tissue. These results demonstrate that striatal but not cortical or mesencephalic brain grafts can promote the restoration of the ability to acquire an inhibitory avoid- ance task and suggest that the acetylcholine tissue con- tent is involved in the behavioral recovery. © 1994 Academic Press, Inc. Several studies have shown that embryonic neural tissue is able to survive transplantation into the adult mammalian brain. The considerable ca- pability of the embryonic tissues to reinnervate and induce functional recovery in the host brain has also been shown (BjSrklund & Stenevi, 1984; Dunnet & Bj6rklund, 1987; Freed, Medinaceli, & Wyatt, 1985). The striatum is probably the most extensively ex- plored region for combined morphological and func- tional studies of intracerebral grafted neurons. i This research was supported by a grant from DGAPA-UNAM IN-204689 and CONACyT (0178-N9107). We thank Oreste Car- bajal for his technical assistance. Address correspondence and reprint requests to F. Berm~dez-Rattoni, Instituto de Fisiologia Celular, UNAM, Apdo. Postal 70-600, 04510 M~xico, D.F. Fax: (525) 622-5607. Either blocks or dissociated cell suspensions of fetal striatal tissue have been shown to survive and dif- ferentiate in the caudate-putamen of adult lesioned rats (Isacson, Brundin, Kelly, Gage, & BjSrklund, 1984; Sanberg, Henault, & Deckel, 1986). Striatal grafts produce recovery of abnormal motor activity and imbalances due to damage of the nigrostriatal pathway (Dunnett, Isacson, Sirinathsinghji, Clarke, & Bj5rklund, 1988; Sanberg et al., 1986) as well as of learning deficits in striatum-lesioned rats such as spatial alternation learning or T-maze (for a re- view see Wictorin, 1992; Deckel, Moran, Coyle, San- berg, & Robinson, 1986). The interference of normal striatal activity by means of electrolytic lesions (Packard & White, 1990; McDonald & White, 1993), microinjections of anticholinergic drugs (Berm~dez-Rattoni, Mdjica- Gonz~lez, & Prado-Alcal~, 1986), or neurotoxins (Sandberg, Sanberg, Hanin, Fisher, & Coyle, 1984) lead to a marked impairment in the acquisition of conditioned responses, i.e., inhibitory avoidance, ra- dial maze learning, or autoshaping conditioning (Bermddez-Rattoni et al., 1986; Packard & White 1990; White, 1989; McDonald & white, 1993). In the present work we have studied the effect of striatal, mesencephalic, and cortical grafts on the recovery of inhibitory avoidance learning in stria- tal-lesioned rats. In addition, immunocytochemistry for tyrosine hydroxylase (TH), acetylcholinesterase (ACHE) histochemistry, and Nissl staining tech- niques were performed on the animals' brains. Seventy male Wistar rats weighing 250-290 g were randomly assigned to one of two groups (con- trol intact rats (Con), n = 20; and lesioned group, n = 50). Two large bilateral electrolytic lesions (2 mA, 1 min) were made under pentobarbital anes- thesia (50 mg/kg) to encompass the dorsal striatum 196 0163-1047/94 $6.00 Copyright © 1994 by Academic Press, Inc. All rights of reproduction in any form reserved.