Social influences on morphine-conditioned place preference in adolescent BALB/cJ and C57BL/6J mice

Abstract

Rationale: Among human adolescents, drug use is substantially influenced by the attitudes and behaviors of peers. Social factors also affect the drug-seeking behaviors of laboratory animals. Conditioned place preference (CPP) experiments indicate that social context can influence the degree to which rodents derive a rewarding experience from drugs of abuse. However, the precise manner by which social factors alter drug reward in adolescent rodents remains unknown.

Objectives: We employed the relatively asocial BALB/cJ (BALB) mouse strain and the more prosocial C57BL/6J (B6) strain to explore whether "low" or "high" motivation to be with peers influences the effects of social context on morphine CPP (MCPP).

Methods: Adolescent mice were conditioned by subcutaneous injections of morphine sulfate (0.25, 1.0, or 5.0 mg/kg). During the MCPP procedure, mice were housed in either isolation (Ih) or within a social group (Sh). Similarly, following injection, mice were conditioned either alone (Ic) or within a social group (Sc).

Results: Adolescent B6 mice expressed a robust MCPP response except when subjected to Ih-Sc, which indicates that, following isolation, mice with high levels of social motivation are less susceptible to the rewarding properties of morphine when they are conditioned in a social group. By contrast, MCPP responses of BALB mice were most sensitive to morphine conditioning when subjects experienced a change in their social environment between housing and conditioning (Ih-Sc or Sh-Ic).

Conclusions: Our findings demonstrate that susceptibility to morphine-induced reward in adolescent mice is moderated by a complex interaction between social context and heritable differences in social motivation.

Fig. 1

Natural preferences of BALB and B6 mice for the conditioning environments. Control mice were subjected to the same procedure as experimental mice, but both of the conditioning environments were paired with saline administration. Both BALB and B6 control mice expressed a natural preference for the conditioning environments. B6 control mice preferred the aspen environment over paper, while BALB control mice preferred the paper environment over aspen. N=46 mice per strain. Dotted vertical lines denote the respective mean for each distribution as reported in the Results section. Data are presented as the total number of mice within each range of preference scores

Fig. 2

MCPP responses of B6 and BALB mice at each dose of morphine. Mice from both the a B6 and b BALB strains developed a preference for the environment paired with the 1.0- and 5.0-mg/kg morphine sulfate doses relative to the preferences of control mice, but only BALB mice expressed a significant preference for the 0.25-mg/kg morphine sulfate dose. *P<0.05, orthogonal contrast with saline. Morphine, N=27–32 mice for each combination of dose and strain; saline, N=46 mice per strain. All data are presented as the mean preference score±standard error of the mean

Fig. 3

MCPP responses of B6 and BALB mice as a function of each housing/conditioning combination. When all morphine doses were combined, MCPP responses of a B6 but not b BALB mice were sensitive to the social environment of housing and conditioning. B6 mice from the Ih–Sc condition expressed a reduced preference for the morphine-paired bedding relative to mice in the Ih–Ic condition, while no difference in preference was observed in BALB mice from different social housing/conditioning groups. *P<0.05, orthogonal contrast. Morphine, N=19–24 mice for each combination of housing/conditioning social environment and strain. All data are presented as the mean preference score±standard error of the mean

Fig. 4

MCPP responses of BALB and B6 mice from each housing/conditioning combination as a function of morphine dose. B6 mice from the a Ih–Ic, c Sh–Ic, and d Sh–Sc housing/conditioning combinations expressed increasing preferences for higher morphine doses. However, B6 mice in the b Ih–Sc condition did not develop a significant CPP for any morphine dose. The MCPP responses of BALB mice were more varied between different housing/conditioning combinations. f, g When the housing/conditioning combination involved a transition between social grouping and isolation (Ih–Sc or Sh–IC), BALB mice exhibited an MCPP for 0.25-mg/kg morphine that was not observed. e, h when the social environment was stable (Ih–Ic or Sh–Sc). BALB mice from both the Ih–Sc and Sh–Ic conditions did not develop MCPP at 1.0- and 5.0-mg/kg morphine, respectively, but these doses elicited an MCPP response in Ih–Ic and Sh–Sc mice. *P<0.05, orthogonal contrast with saline. Ns morphine=6–10 mice per strain for each housing/conditioning and morphine dose; saline=46 mice per strain. All data are presented as the mean preference score ± standard error of the mean