Rationale: Interstrain differences in the motivational properties of morphine and heroin have been previously reported in mice, suggesting the involvement of a genotype-dependent modulation of the rewarding effects of opiates. Yet, interstrain differences in the motivational effects of naloxone have not been described.
Objectives: The aim of our study was to examine genotype modulation of the motivational effects of opiates in inbred stains of mice with known, distinct, opiate-induced phenotypes, and morphine-induced striatal transcriptional responses.
Methods: We studied the rewarding properties of morphine (5, 10, and 20 mg/kg i.p.) and heroin (1, 5, and 10 mg/kg i.p.) in conditioned place preference (CPP) as well as the aversive properties of naloxone (1, 10, and 20 mg/kg i.p.) in the conditioned place aversion (CPA) paradigm in C57Bl/6J (C57), DBA/2J (DBA), and SWR/J (SWR) inbred strains of mice.
Results: Our results show that morphine and heroin as well as naloxone induce CPP and CPA, respectively, in a genotype- and dose-dependent manner in these studied inbred strains of mice. Interestingly, C57 mice are the most sensitive in the case of the rewarding properties of morphine and heroin but are the least sensitive to the aversive effects of naloxone, whereas the DBA strain exhibit the opposite behavioral effects.
Conclusions: We suggest that motivational homeostasis can be modulated by mu opioid receptors in mice, with the C57 mice representing a genotype that is more sensitive to processes related to rewards, whereas the genotype of DBA is more sensitive to aversion.