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.

Early social isolation increases persistence of alcohol-seeking behavior in alcohol-related contexts

“…Whitaker et al (2013) showed that isolation during adolescence had an effect that was similar to that of repeated drug exposure, in that isolation enhanced the long-term potentiation of N-methyl-Daspartate receptor-mediated glutamatergic transmission in dopaminergic neurons. Such neurophysiological changes may explain the effects of isolation on learning about reinforcer-related stimuli that have been reported in previous studies of drugs (Zakharova et al, 2009;Kennedy et al, 2012) and SUC (Harmer and Phillips, 1998;van Den Berg et al, 1999). Nevertheless, more studies are needed to explore the relationship between the physiological and behavioral effects of early isolation to better understand the way in which social conditions affect processes that are linked to drug addiction.…”

Emotional valence and context of social influences on drug abuse-related behavior in animal models of social stress and prosocial interaction

“…For instance, Hall et al (1998) found that both alcohol and sucrose consumption are increased in isolation-reared rats, although in contrast, others have found no change or a transient decrease in sucrose consumption (Bardo et al 2001; McCool and Chappell 2009). Early research examining effects of isolation rearing on drug-CPP suggest that sensitivity to opiate and stimulant reward is either reduced or unchanged relative to that observed in social-reared controls (Bowling and Bardo 1994; 1985; 1983; 1986; Wongwitdecha and Marsden 1996), in contrast to more recent studies suggesting enhanced sensitivity (Kennedy et al 2011; Zakharova et al 2009). The reason for these discrepancies is likely related to the apparatus.…”

“…The ability to see other animals during conditioning introduces a social component (Gipson et al 2011b) that may have interfered with conditioning in the isolation-reared rats relative to controls. Importantly, the enhanced sensitivity to opiate reward reported by Kennedy et al (2011) is due to an interaction between isolation rearing and the genetic propensity for social behavior in mice to influence morphine-CPP. In the relatively social mouse strain (C57BL/6J), the dose-effect function for morphine-CPP was similar in isolate- and social-reared mice, but in a less social strain (BALB/cJ), the isolation-reared mice showed greater morphine-CPP at a high, but not a low, dose relative to social-reared mice.…”

“…Similarly, morphine-CPP is attenuated in mice conditioned with a conspecific, and this effect is more robust in singly housed mice than socially housed mice (Kennedy et al 2011). …”

Individual Differences and Social Influences on the Neurobehavioral Pharmacology of Abused Drugs

“…Morphine facilitates social interaction, including play behavior (Normansell and Panksepp, 1990), yet sensitization of morphine-induced locomotor activity is attenuated in mice that receive morphine in a social context (Procopio-Souza et al, 2011). Similarly, using a highly social strain of mice (C57BL/6J), morphine CPP is inhibited in male mice when conditioning occurs in a social context compared with an isolated context (Kennedy et al, 2012). No influence of social context is observed in male mice that are socially housed.…”