Neuroscience Letters, 68 (1986) 127-133 127 Elsevier Scientific Publishers Ireland Ltd. NSL 04029 EFFECTS OF DOPAMINE-RICH GRAFTS ON CONDITIONED ROTATION IN RATS WITH UNILATERAL 6-HYDROXYDOPAMINE LESIONS S.B. DUNNETT I*, I.Q. WHISHAW 2, G.H. JONES l and O. ISACSON ~ ~Department q/ Experimental Psycholo,~.v, UniversiO' of Cambridge, Cambridge (U.K.), :D~7~artment o/ PsycholoKr, University qf Lethbridge, Lethbridge, A lta. (Canada) and 3Department qf HistaloLo', (:niversit v of Luml, l, und (Sweden) (Received March 19th. 1986; Revised version received April 10th, 1986: Accepted April 1 lth, 1986l Key wm'dw conditioned rotation - dopamine 6-hydroxydopamine transplant To assess the capacity of dopamine-rich grafts to ameliorate conditioned behavioural deficits induced by dopamine depleting lesions, rats with unilateral 6-hydroxydopamine lesions and intrastriatal grafts were compared with rats with lesions alone and with unoperated control rats in learning a conditioned turning response ('conditioned rotation') for water. The lesions impaired conditioned contralateral rotation and the grafts ameliorated the impairment. By contrast, the grafts introduced an ipsilateral im- pairment which was not apparent in the rats with lesions alone. The results show that some aspects of graft flmction are adaptive, but that other aspects of function are not well controlled by the host brain, and so may be maladaptive. Grafts of embryonic ventral mesencephalon containing the developing dopamine cells of the substantia nigra have been found to ameliorate some of the spontaneous and drug-induced behavioural deficits associated with 6-hydroxydopamine (6- OHDA) lesions of intrinsic mesotelencephalic dopaminergic systems in the adult rat forebrain [5, 7]. Conditioned behaviours have also been found to be disrupted by dopaminergic lesions, although there is disagreement about whether this is attribut- able to a disruption of learning per se, or to an inability to execute the learned re- sponses [3, 4, 6, 11, 14]. We wished to investigate whether dopamine-rich grafts might ameliorate deficits in conditioned behaviours induced by dopamine-denervating lesions. To avoid the severe regulatory and motivational problems associated with bilateral 6-OHDA lesions, we have used unilateral lesions with the conditioned rotation paradigm, first described by Yamamoto and Freed l! 5], in which thirsty rats are trained to turn in a designated direction for water reinforcement. Conditioned rotation is associated with an increase in dopamine concentration and turnover in the contralateral neostriatum [15], and lesions of the contralateral (but not the ipsila- teral) mesotelencephalic dopamine pathway disrupt performance in the task [4]. Seventeen young adult female rats of the Sprague-Dawley strain received unila- *Author for correspondence at: Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, U.K. 0304-3940/86'$ 03.50 © 1986 Elsevier Scientific Publishers Ireland Ltd.