Maternal deprivation and handling modify the effect of the dopamine D3 receptor agonist, BP 897 on morphine-conditioned place preference in rats

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-conditioned 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.