Neurotoxicity Research, 2002 VoL.4, pp. 503-522 t•ll•aY IOr&Francis healthsciences Functional Deficits Following Neonatal Dopamine Depletion and Isolation Housing: Circular Water Maze Acquisition Under Pre-exposure Conditions and Motor Activity TREVOR ARCHER a'*, TOMAS PALOMO b and ANDERS FREDRIKSSONc ~Department of Psychology, University of G6teborg, P.O. Box 500, SE-40530 Gi~teborg, Sweden; bServicio de Psiquiatria, Hospital 12 de Octobre, Ctra. Andalucia Kin. 5,400, 28041, Madrid, Spain; CDepartment of Neuroscience, University of Uppsala, Psychiatry Ullerdker, SE-75017 Uppsala, Sweden (Received 20 November 2001; Revised 11 April 2002; In final form 17 April 2002) Seven experiments and several behavioural tests were performed to study the effects of housing condition and experimental test conditions upon the behavioural responses and performance of adult rats neonatally treated with 6-hydroxydopamine (6-OHDA, 100ug intracisternally, i.c.) or with vehicle. Postnatal 6-OHDA induced locomotor and total activity hyper- activity and deficits in navigational learning in a circular swim maze that were blocked by pre-treatment with a dopamine (DA) reuptake inhibitor but not a noradrenaline (NA) reuptake inhibitor. Isolation-hou- sing induced deficits in maze learning performance. Grouped housing improved the maze learning per- formance of 6-OHDA treated rats whereas vehicle treated rats that were isolation housed performed better following latent learning (LL) pre-exposure trials. 6-OHDA treated rats that received both Grouped housing and latent learning trials performed better on the spatial navigation task than those that received Grouped housing but no latent learning or Isolation housing and latent learning. Analysis of habituation quotients indicated marked deficits by 6-OHDA-treated rats suggesting inability to acquire this simple, nonassociative form of learning. Methylphenidate increased all three parameters of motor activity: locomotion, rearing and total activity, in both Iso- lation-housed and Group-housed rats from 60- to 90- or 120-min post-injection. NDO 008 induced variable and parameter-dependent effects: locomotion was elevated initially in both Isolated and Grouped rats by the compound and then reduced in the Isolated rats only whereas total activity was only elevated initially in the Isolated rats and unaffected in the Grouped rats. Rearing behaviour was reduced markedly, directly post-injection, in the Isolation-housed rats. DA, DOPAC and HVA concentrations in the striatum, nucleus accumbens, olfactory tubercle and midbrain were reduced but most markedly in the striatum. 5-Hydroxytryptamine (5-HT) and 5-hydroxyindole *Corresponding author. Tel.: +46-31-7734694. Fax: +46-31-7734628. ISSN1029-8428 print/ISSN 1476-3524 online 9 2002Taylor & FrancisLtd DOI: 10.1080/1029842021000022098 acetic acid (5-HIAA) concentrations were elevated in the striatum, nucleus accumbens (not 5-HIAA) and olfactory tubercle. Keywords: 6-Hydroxydopamine; Grouped; Isolation; Latent learning; Habituation; Methylphenidate; NDO 008; Dopamine; Serotonin; Sprague-Dawley rats INTRODUCTION 6-Hydroxydopamine (6-OHDA) has been applied usefully in both adult (Ungerstedt, 1971; Breese and Traylor, 1972) and neonate (Creese and Iversen, 1973; Shaywitz et al., 1976a; Shaywitz and Pearson, 1978) rats to study the behavioural effects of loss of mesencephalic dopamine (DA) neurons. Destruction of these neurons in newborn rats through intracerebral, i.e. intracisternal (i.c.) or intracerebroventricular (i.c.v.), administration of 6-OHDA induces behavioural changes characteri- sed by: (1) hyperactivity in tests of spontaneous motor activity and/or exploratory behaviour, that may or may not persist into adulthood but generally have been found to do so (Smith et al., 1973; Shaywitz et al., 1976b; 1977; Erinoff et al., 1979; Fobs and Olds, 1981; Miller et al., 1981; Archer et al., 1988; 1990; Archer, 1989; Luthman et al., 1989a,b; 1991; 1995; 1997; Archer and Fredriksson, 1992), (2) retarded or impaired acqui- sition of instrumental learning tasks, such as ope- rant lever pressing on a fixed ratio schedule for E-mail: trevor.archer@psy.gu.se