Dopamine receptor D1 but not D3 essential for morphine-induced conditioned responses

Recent studies indicate the involvement of dopamine receptors D1 and D3 in the regulation of locomotor stimulant and conditioned responses to morphine in mice. Moreover, expression of brain-derived neurotrophic factor (BDNF) may be modulated by D1 and D3 receptor activities in the nucleus accumbens (NAc) and prefrontal cortex (PFC). However, the underlying interactions between D1 and D3 receptors and BDNF in the expression of behavioral responses controlled by drug-associated cues have not yet been fully elucidated. In this study, we used dopamine receptor mutant mice to explore the roles of the D1 and D3 receptors in locomotion and morphine-induced place preference; furthermore, we investigated the effects of morphine on BDNF expression in the NAc and PFC of the mouse brain. Our results show that D1 receptor but not D3 receptor mutant mice had decreased sensitivity to acute morphine-induced (10 mg/kg) locomotion (D1: 3814.82 +/- 319.9 cm vs D3: 8089.64 +/- 967.4 cm). Furthermore, D1 receptor mutant mice did not acquire morphine-conditioned place preference (D1: -18.3 +/- 59.9, D3: 217.7 +/- 64.1) and showed decreased BDNF expression in the NAc (D1: 0.33 +/- 0.07 fold, D3: 2.21 +/- 0.18 fold) and PFC (D1: 0.74 +/- 0.15 fold, D3: 1.68 +/- 0.22 fold) compared with wild-type and D3 receptor mutant mice. These findings suggest that the D1 receptor is necessary for the induction of cue-associated morphine seeking and modulates locomotor habituation processes in response to acute morphine. The dopamine receptor D1 but not the D3 is also critical for morphine-induced BDNF expression in the NAc and PFC.