Neuroscience Vol. 38, No.3, pp. 655466, 1990 Printed in Great Britain 0306-4522/90 $3.00 + 0.00 Pergamon Press plc 0 1990 IBRO zyxwvut MOTOR IMPAIRMENTS AND NEUROCHEMICAL CHANGES AFTER UNILATERAL 6-HYDROXYDOPAMINE LESION OF THE NIGROSTRIATAL DOPAMINERGIC SYSTEM IN MONKEYS P. APICELLA,* E.TROUCHE,A.NIFKXJLLON, E. LEGALLET and N. DUSTICIER Laboratoire de Neurosciences Fonctionnelles, CNRS, B.P. 71,31 chemin Joseph Aiguier, 13402 Marseille Cedex 9, France Almtraet-Unilateral lesions of the nigrostriatal dopaminergic system were induced in five monkeys by intranigral injections of the neurotoxin 6-hydroxydopamine. Following the lesion, all monkeys showed a transient reluctance in using the contralateral forelimb, accompanied, in two monkeys by semi-flexed posture of the disabled forelimb. Three of the monkeys that had been conditioned to perform a visually triggered goal-directed arm movement, showed an increase in latency and duration of contralateral arm movements. Task performance recovered spontaneously to preoperative levels within four months in two monkeys despite significant reductions of endogenous dopamine and dihydroxyphenylacetic acid contents in the caudate nucleus, putamen and globus pallidus ipsilateral to the neurotoxic nigral injection. The third monkey exhibited a persistent increase in movement latency associated with a near complete loss of dopamine in both the putamen and the caudate nucleus. In all cases, an increase in the dihydroxyphenyl- acetic acid to dopamine ratio was detected in the striatum and pallidum suggesting a compensatory increase in dopamine turnover in remaining intact dopaminergic nerve terminals. The level of serotonin was changed in all monkeys consisting of either a decrease or an increase, depending on the striatopallidal regions studied. Changes in choline acetyltransferase and glutamic acid decarboxylase activities in the same regions were only seen in some cases. The present results show that 6-hydroxydopamine-induced partial unilateral lesion of nigral dopaminergic neurons produced predominantly contralateral hypo- kinesia, accompanied by reductions of dopamine content in the ipsilateral striatum and pallidum. The use of this locally applied neurotoxin appears to be a suitable method for investigating neurophysiological mechanisms underlying hypokinesia since deficits in both initiating and executing movements can be expressed independently of other behavioral symptoms. The results show more persistent deficits in starting movements than in their execution and thus suggest that motor initiation is more dependent upon the functional integrity of the nigrostriatal dopamine system than movement completion. Hypokinesia is one of the most prominent motor symptoms observed after experimental electrolytic lesions of the substantia nigra (SN) in mon- keys. 16~35,36,4* Morphological and neurochemical data have confirmed that the loss of dopaminergic neurons from the pars compacta of the SN parallels depletion of dopamine (DA) in the striatum (caudate nucleus and putamen). 20,36,43 Alleviation of hypokinetic symptoms by administration of DA agonists further suggests the involvement of dopaminergic trans- mission in these motor deficits.‘6s35 The effects of striatal DA depletion using the selective catecholamine neurotoxin B-hydroxy- dopamine (6-OHDA) were so far extensively studied *To whom correspondence should be addressed. Abbreviurions: ChAT, choline acetyltransferase; DA, dopamine; DOPAC, dihydroxyphenylacetic acid; GAD. glutamate decarboxylase; GPei-globus pallidus, external segment; GPi, globus pallidus, internal segment: S-HT. 5-hydroxytryptamine iserotonin); MPTPY I-methyl4: phenyl-1,2,3,6-tetra hydropyridine; MT, movement time; 6-OHDA, 6-hydroxydopamine; RT, reaction time; SN, substantia nigra; TH, tyrosine hydroxylase. in rats. Unilateral injections of this neurotoxin into the rat SN produces typical behavioral disturbances, such as postural asymmetry, hypokinesia and con- tralateral “sensory neglect”.28*30 Studies in monkeys only concerned the clinical deficits and effects of pharmacological treatment after 6-OHDA-induced striatal DA depletion.” Quantitative assessments of motor performance after striatal DA depletion were conducted in conditioned monkeys after unilateral electrolytic lesions in SN2’,48or systemic injections 1-methyl - 4-phenyl- 1,2,3,6_tetrahydropyridine $PTP). ‘3.42 The unilateral injection of 6-OHDA into the SN represents an appropriate method for study- ing hypokinesia following striatal DA depletion. This lesion causes none of the additional behavioral im- pairments which would interfere with task perform- ance (such as rigidity, tremor, aphagia and adipsia). Moreover, the deficits should be predominantly re- stricted to one side of the body, thus allowing the intact side to serve as reference. Previous results from our laboratory have shown that unilateral 6-OHDA- induced lesion of the nigrostriatal DA system in conditioned monkeys produces latency increases of 655