ORIGINAL INVESTIGATION Maternal deprivation and handling modify the effect of the dopamine D3 receptor agonist, BP 897 on morphine-conditioned place preference in rats Vincent Vazquez & Stéphanie Weiss & Bruno Giros & Marie-Pascale Martres & Valérie Daugé Received: 3 August 2006 / Accepted: 3 April 2007 / Published online: 10 May 2007 # Springer-Verlag 2007 Abstract Rationale Maternal deprivation and handling can lead to a vulnerability to opiate dependence. However, the involvement of the dopamine D3 receptors has not been investigated. Objectives This study analysed the effects of a selective partial D3 receptor agonist, BP 897, on morphine-condi- tioned place preference (CPP) in deprived and handled rats. Materials and methods The effects of BP 897 were studied on the expression and the extinction of morphine CPP. Quantitative autoradiography of D2, D3 receptors and immunoautoradiography of dopamine transporter were performed in some saline- and morphine-treated rats 24 h after the place preference test. Results Morphine (5 mg/kg) induced a more prolonged morphine CPP in deprived and handled rats than in control animals. BP 897 (0.5 or 2 mg/kg) enhanced the expression of morphine conditioning in control rats. Same doses did not change morphine conditioning in deprived rats. BP 897 (2 mg/kg) suppressed morphine CPP in handled rats. An increase in basal D2 receptor density in the mesencephalon of handled rats, which was suppressed after morphine CPP, was observed. A decrease in D2 receptor levels in morphine-treated deprived rats occurred in the nucleus accumbens. Conclusions This study shows that maternal deprivation and handling induced a prolonged morphine CPP, and different changes of D2/D3 receptor functioning revealed after morphine CPP. Early manipulations of infant–mother relationships may have different consequences on the balance of opioidergic and dopaminergic neurotransmission and may be of interest to reveal pharmacological properties of dopamine receptor partial agonists or antagonists potentially useful for therapeutic applications. Keywords Maternal deprivation . Handling Place preference paradigm . Morphine D3 partial agonist BP 897 . DAT . D2 . D3 receptors . Rat Introduction Long maternal separation in rodents has been shown to lead to anxiety, stress-induced illness and depression (reviewed in Anisman et al. 1998; Hall 1998; Francis et al. 1999; Matthews and Robbins 2003). A vulnerability to drug dependence as a direct long-term behavioural consequence of disruption of the infant–mother relation- ships has also been documented. Some data showed that separated rats develop a preference to ethanol (Huot et al. 2001; Ploj et al. 2003; but see also Marmendal et al. 2004; Jaworski et al. 2005) and increase (Kosten et al. 2000, 2005; Zhang et al. 2005) or decrease (Matthews et al. 1999) the acquisition of cocaine self-administration. In addition, a hypersensitivity of separated rats to psychostimulant-induced hyperlocomotor activity and modifications of dopaminergic systems have been reported (Kehoe et al. 1996; Hall et al. 1999; Brake et al. 2004). More recently, we have shown that Psychopharmacology (2007) 193:475–486 DOI 10.1007/s00213-007-0789-9 V. Vazquez : S. Weiss : B. Giros : M.-P. Martres : V. Daugé Laboratoire de Neurobiologie et Psychiatrie, Faculté de Médecine, Inserm U513, 8 rue du Général Sarrail, Créteil 94010, France V. Vazquez : S. Weiss : B. Giros : M.-P. Martres : V. Daugé (*) Laboratoire de Neurobiologie et Psychiatrie, Faculté de Médecine, Université Paris XII, 8 rue du Général Sarrail, Créteil 94010, France e-mail: valerie.dauge@creteil.inserm.fr