Long-term treatments with dopaminergic agents are associated with adverse effects, including augmentation. Augmentation consists of an exacerbation of restless legs syndrome (a sleep-related movement disorder) symptoms during treatment compared to those experienced during the period before therapy was initiated. The objective of this study was to examine locomotor activity in rats after long-term dopaminergic treatment and its relationship with expression of the D2 receptor, in addition to demonstrating possible evidence of augmentation. The rats were divided into control (CTRL) and drug (Pramipexole—PPX) groups that received daily saline vehicle and PPX treatments, respectively, for 71 days. The locomotor behavior of the animals was evaluated weekly in the Open Field test for 71 days. The expression of the dopamine D2 receptor was evaluated by Western Blot analysis. The animals that received the PPX demonstrated a significant reduction in locomotor activity from day 1 to day 57 and a significant increase in immobility time from day 1 to day 64 relative to baseline values, but these values had returned to baseline levels at 71 days. No changes in the expression of the D2 receptor were demonstrated after treatment with a dopaminergic agonist. This study suggests changes in locomotor activity in rats after long-term PPX treatment that include an immediate reduction of locomotion and an increase in immobilization, and after 64 days, these values returned to baseline levels without evidence of augmentation. In addition, it was not possible to demonstrate a relationship between locomotor activity and the expression of D2 receptors under these conditions.7420320830850004; NSFC; National Natural Science Foundation of ChinaEarley, C.J., Silber, M.H., Restless legs syndrome: Understanding its consequences and the need for better treatment (2010) Sleep Med, 11 (9), pp. 807-815Allen, R.P., Earley, C.J., Augmentation of the restless legs syndrome with carbidopa/levodopa (1996) Sleep, 19, pp. 205-213Winkelman, J.W., Johnston, L., Augmentation and tolerance with long-term pramipexole treatment of restless legs syndrome (RLS) (2004) Sleep Med., 5, pp. 9-14Chokroverty, S., Long-term management issues in restless legs syndrome (2011) Mov. Disord., 26, pp. 1378-1385Paulus, W., Schomburg, E.D., Dopamine and the spinal cord in Restless Legs Syndrome: Does spinal cord physiology reveal a basis of augmentation? Sleep Med (2006) Rev., 10, pp. 185-196Ondo, W., Romanyshyn, J., Vuong, K.D., Lai, D., Long-term treatment of restless legs syndrome with dopamine agonists (2004) Arch. Neurol., 61, pp. 1393-1397Chernoloz, O., El Mansari, M., Blier, P., Sustained administration of pramipexole modifies the spontaneous firing of dopamine, norepinephrine, and serotonin neurons in the rat brain (2009) Neuropsychopharmacology, 34 (3), pp. 651-661Luo, F., Li, C., Ondo, W.G., Xu, P., Xie, W., Le, W., The long-term effects of the dopamine agonist pramipexole in a proposed restless legs syndrome animal model (2011) Sleep Med., 12, pp. 41-46Broadhurst, P.L., Experiments in psychogenetics: Applications of biometrical genetics to the inheritance of behaviour (1960) Experiments in Personality, 1. , Eysenck HJ, London: Routledgc & Kegan PaulQu, S., Le, W., Zhang, X., Xie, W., Zhang, A., Ondo, W.G., Locomotion is increased in A11-lesioned mice with iron deprivation: A possible animal model for restless legs syndrome (2007) J. Neuropathol. Experimental Neurol., 66, pp. 383-388Fukushiro, D.F., Calzavara, M.B., Trombin, T.F., Lopez, G.B., Abílio, V.C., Andersen, M.L., Tufik, S., Frussa-Filho, R., Effects of environmental enrichment and paradoxical sleep deprivation on open-field behavior of amphetamine-treated mice (2007) Physiol. Behav., 92, pp. 773-779Becker, P.M., Ondo, W., Sharon, D., Encouraging initial response of restless legs syndrome to pramipexole (1998) Neurology, 51, pp. 1221-1223Scholz, H., Trenkwalder, C., Kohnen, R., Kriston, L., Riemann, D., Hornyak, M., Dopamine agonists for the treatment of restless legs syndrome (2011) Cochrane Database of Systematic Reviews, (3). , CD006009.pub2Ferini-Strambi, L., Restless legs syndrome augmentation an pramiprexole treatment (2002) Sleep Med., 3, pp. S23-S25Silber, M., Girish, M., Izurieta, R., Pramipexole in the management of restless legs syndrome: An extended study (2003) Sleep, 26, pp. 819-821García-Borreguero, D., Allen, P., Benes, H., Earley, C., Happe, S., Högl, B., Kohnen, R., Winkelmann, J., Augmentation as a treatment complication of restless legs syndrome: Concept and management (2007) Mov. Disord., 22, pp. 476-484Cervenka, S., Palhagen, S.E., Comley, R.A., Panagiotidis, G., Cselenyi, Z., Matthews, J.C., Lai, R.Y., Farde, L., Support for dopaminergic hypoactivity in restless legs syndrome: A PET study on D2-receptor binding (2006) Brain, 129, pp. 2017-2028Fleetwood-Walker, S.M., Hope, P.J., Mitchell, R., Antinociceptive actions of descending dopaminergic tracts on cat and rat dorsal horn somatosensory neurons (1988) J. Physiol., 399, pp. 335-348Hartesveldt, C.V., Temporal and environmental effects on quinpirole-induced biphasic locomotion in rats (1997) Pharmacol. Biochem. Behav., 58, pp. 955-960Zhuang, X., Oosting, R.S., Jones, S.R., Hyperactivity and impaired response habituation in hyperdopaminergic mice (2001) Proc. Natl. Acad. Sci. USA, 98, pp. 1982-1987Esteves, A.M., Lopes, C., Frussa-Filho, R., Frank, M.K., Cavagnolli, D., Arida, R.M., Tufik, S., de Mello, M.T., Spontaneously hypertensive rats: Possible animal model of sleep-related movement disorders (2013) J. Mot. Behav., 45 (6), pp. 487-493