ENRICHED ENVIRONMENT IMPROVES MOTOR FUNCTION IN INTACT AND UNILATERAL DOPAMINE-DEPLETED RATS N. M. JADAVJI, B. KOLB AND G. A. METZ* Canadian Centre for Behavioural Neuroscience, University of Leth- bridge, 4401 University Drive, Lethbridge, Alberta, Canada T1K 3M4 Abstract—Previous studies have suggested that experience and environmental conditions can affect the progression and severity of symptoms in Parkinson’s disease. Furthermore, earlier reports have indicated that enriched environment pro- motes the survival of dopaminergic grafts in a rat model of Parkinson’s disease. Here we investigated whether environ- mental enrichment affects normal motor function and the severity of dopamine depletion in a rat model of Parkinson’s disease. Adult female Long-Evans rats were pre-trained and tested daily in a skilled reaching task. One group of rats was placed in an enriched environment while one group was housed under standard conditions. During this time period, reaching success of animals exposed to the enriched envi- ronment improved as compared with animals living in stan- dard housing. The animals remained in the two housing con- ditions for six weeks prior to receiving unilateral infusion of the neurotoxin 6-hydroxydopamine into the nigrostriatal bun- dle. The daily behavioral testing continued up to four weeks after lesion. The observations showed that rats housed in an enriched environment significantly improved in reaching success during the first three weeks after lesion as compared with rats housed in the standard condition. Qualitative move- ment analysis, drug-induced rotation and histological find- ings indicate that compensatory processes in particular might have accounted for the behavioral improvements. These data are discussed in relation to possible mechanisms of experience-dependent modulation of the pathology of Par- kinson’s disease. © 2006 IBRO. Published by Elsevier Ltd. All rights reserved. Key words: 6-hydroxydopamine, rat model, environmental enrichment, skilled movement, rotation, recovery. Parkinson’s disease (PD) is a progressive neurological disease mainly associated with aging. The progressive loss of dopaminergic neurons in the midbrain produces a variety of motor symptoms, including tremor, rigidity and impairments of skilled limb movements (Gelb et al., 1999; Jackson et al., 2000; Moore, 2003). Although the pathology of PD has been widely investigated, the fac- tors involved in the progression of the disease are still not well understood (Moore, 2003). While there is a large individual variation of the course and symptoms of PD (Fawcett et al., 2001), environmental factors and lifestyle have been suggested to influence the neurode- generative processes that underlie this condition (Young et al., 1999; Dobrossy and Dunnett, 2004). For example, the incidence of PD might be influenced by educational achievement (Frigerio et al., 2005) and physical exer- cise (Chen et al., 2005). Thus, it can be hypothesized that the pathological processes of PD might also be modulated by enriched environment (EE). EE provides both inanimate and social stimulation (Bezard et al., 2003) and has been shown to enhance structural and functional recovery after brain damage in rats (Diamond et al., 1966; Whishaw et al., 1986a; Kolb and Gibb, 1991; Kolb et al., 1998; Johansson et al., 1999). In particular, rat studies showed that a stimulating environ- ment, such as EE, promotes neuronal plasticity and glial cell proliferation (Pham et al., 2002; Bezard et al., 2003). The enhanced structural plasticity is accompanied by im- provement in motor function, including skilled walking and climbing (Ohlsson and Johansson, 1995; Johansson, 1996; Risedal et al., 2002) and skilled reaching (Biernaskie and Corbett, 2001). While most research on EE has fo- cused on recovery from ischemic brain damage or aging processes (Mohammed et al., 1990; Pham et al., 1999; Biernaskie and Corbett, 2001), previous studies have also indicated that EE has beneficial effects on dementia asso- ciated with PD in humans (Pham et al., 1999; Young et al., 1999). Accordingly, EE was shown to increase neurogen- esis and expression of neurotrophic factors that might exert protective effects in neurodegenerative conditions, such as PD (Ickes et al., 2000; Pham et al., 2002; Bezard et al., 2003). Studies in rat models of PD showed that EE increases the survival of dopaminergic grafts (Dobrossy et al., 2000; Dobrossy and Dunnett, 2004). These findings suggest that EE might exert neuroprotective effects on dopaminergic neurons and preserve motor function in rats with dopamine depletion. The purpose of the present study was to investigate the effects of EE on normal motor function and the pathol- ogy of PD in a rat model. Animals were placed in an EE prior to a unilateral dopamine-depleting lesion induced by the neurotoxin 6-hydroxydopamine (6-OHDA). The ani- mals were tested daily in a skilled reaching task and at regular intervals in a comprehensive test battery to assess a time course of changes in motor function. Animals housed in standard environment (SE) served as a control group. The results reveal that motor symptoms of rats exposed to EE improve permanently during the third week post-lesion. These observations are discussed with re- spect to the influence of EE on neuronal and functional capacities after dopamine depletion. *Corresponding author. Tel: +1-403-394-3992; fax: +1-403-329-2775. E-mail address: gerlinde.metz@uleth.ca (G. A. Metz). Abbreviations: BDNF, brain derived-neurotrophic factor; EE, enriched environment; PD, Parkinson’s disease; SE, standard environment; TH, tyrosine hydroxylase; 6-OHDA, 6-hydroxydopamine. Neuroscience 140 (2006) 1127–1138 0306-4522/06$30.00+0.00 © 2006 IBRO. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.neuroscience.2006.03.027 1127