Socially induced morphine pseudosensitization in adolescent mice

Hodgson, Stephen R.; Hofford, Rebecca S.; Roberts, Kris W.; Wellman, Paul J.; Eitan, Shoshana

doi:10.1097/fbp.0b013e328337be25

Cited by 24 publications

(18 citation statements)

References 83 publications

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“…While most studies focus on humans, some studies suggest that in rodents there may also be a social effect on alcohol preference and consumption from interaction with intoxicated peers (Fernández-Vidal and Molina, 2004; Hunt et al, 2001). Similarly, we recently observed that social interactions with morphine-treated mice resulted in an enhanced hyper-locomotion response to morphine in drug-naïve adolescent male mice (Hodgson et al, 2010). …”

Section: Introductionmentioning

confidence: 65%

Social influences on morphine sensitization in adolescent females

Hofford¹,

Roberts²,

Wellman³

et al. 2010

Drug and Alcohol Dependence

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We recently observed that social interactions influence morphine responsiveness in adolescent males. Given sex-related differences in both social interactions and responses to morphine, the present study examines social influences on morphine sensitization in adolescent female mice. Four experimental groups were examined: [1] morphine-treated mice (twice daily, 10-40 mg/kg, s.c.) housed physically and visually separated from saline-treated mice ('morphine only'), [2] morphine-treated mice housed together with saline-treated mice ('morphine cage-mates (of saline)'), [3] saline-treated mice housed together with morphine-treated mice ('saline cage-mates (of morphine)'), and [4] saline-treated mice housed physically and visually separated from morphine-treated mice ('saline only'). Following the treatment period, mice were tested individually for their locomotor response to 20 mg/kg morphine (s.c.). There were no significant differences in morphine-induced hyper-locomotion between saline only and saline cage-mates (of morphine) female adolescent mice. Notably, morphine only mice exhibited significantly greater morphine sensitization as compared to morphine cage-mates (of saline). Thus, this study demonstrates social influences on morphine sensitization in adolescent females. Drug use during early adolescence is a key predictor of later drug abuse and dependence during adulthood. Thus, understanding the specific vulnerabilities to drug use in this age group may represent a first step in helping develop more effective treatment programs.

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Section: Introductionmentioning

confidence: 65%

Social influences on morphine sensitization in adolescent females

Hofford¹,

Roberts²,

Wellman³

et al. 2010

Drug and Alcohol Dependence

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“…The enhanced sensitivity of mice from the B6 strain to changes in the state of a conspecific has also been demonstrated in a behavioral paradigm where B6 mice, but not BALB mice, were responsive to conspecific distress (Chen et al, 2009). In addition, B6 mice that have never been directly exposed to morphine can be sensitized to morphine-induced hyper-locomotion through exposure to morphine-treated littermates (Hodgson et al, 2010b). Interestingly, this social responsiveness was expressed by adolescents, but not by adults.…”

Section: Discussionmentioning

confidence: 99%

Age-dependent and strain-dependent influences of morphine on mouse social investigation behavior

Kennedy

Panksepp

Wong³

et al. 2011

Behavioural Pharmacology

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Opioid-coded neural circuits play a substantial role in how individuals respond to drugs of abuse, and most individuals begin using such drugs during adolescence and within a social context. Several studies indicate that adolescent mice exhibit a heightened sensitivity to the effects of morphine, the prototypical opiate drug, when compared with adults, but it is unclear whether these developmental differences are related to aspects of motivated behavior. Moreover, exposure to opioids within the rodent brain can alter the expression of social behavior, yet little is known about whether this relationship changes as a function of development or genetic variation. In this study, we conducted a series of experiments to characterize the relationship between genetic background, adolescent development and morphine-induced changes in mouse social investigation (SI). At two time-points during adolescent development (postnatal day [PD] 25 and 45), social interactions of test mice of the gregarious C57BL/6J (B6) strain were more tolerant to the suppressive effects of morphine (ED50 = 0.97 and 2.17 mg/kg morphine, respectively) than test mice from the less social BALB/cJ (BALB) strain (ED50 = 0.61 and 0.91 mg/kg morphine, respectively). By contrast, this strain-dependent difference was not evident among adult mice on PD 90 (ED50 = 1.07 and 1.41 mg/kg morphine for BALB and B6 mice, respectively). An additional experiment demonstrated that the ability of morphine to alter social responsiveness was not directly related to drug-induced changes in locomotor behavior. Finally, administration of morphine to stimulus mice on PD 25 reduced social interaction of test mice only when individuals were from the B6 genetic background. Overall, these results indicate that alterations in endogenous opioid systems are related to changes in SI that occur during adolescence and that morphine administration may mimic the rewarding nature of SI.

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“…vocal communication, imitation, and empathy) 10–12 that are the hallmarks of sociality. As in several other species including humans, OT has been linked to social behaviors in mice 7 .…”

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confidence: 99%

Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin

Dölen

Darvishzadeh

Huang

et al. 2013

Nature

971

860

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Social behaviors in species as diverse as honey bees and humans promote group survival but often come at some cost to the individual. Although reinforcement of adaptive social interactions is ostensibly required for the evolutionary persistence of these behaviors, the neural mechanisms by which social reward is encoded by the brain are largely unknown. Here we demonstrate that in mice oxytocin (OT) acts as a social reinforcement signal within the nucleus accumbens (NAc) core, where it elicits a presynaptically expressed long-term depression of excitatory synaptic transmission in medium spiny neurons. Although the NAc receives OT receptor-containing inputs from several brain regions, genetic deletion of these receptors specifically from dorsal raphe nucleus, which provides serotonergic (5-HT) innervation to the NAc, abolishes the reinforcing properties of social interaction. Furthermore, OT-induced synaptic plasticity requires activation of NAc 5-HT1b receptors, the blockade of which prevents social reward. These results demonstrate that the rewarding properties of social interaction in mice require the coordinated activity of OT and 5-HT in the NAc, a mechanistic insight with implications for understanding the pathogenesis of social dysfunction in neuropsychiatric disorders such as autism.

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Socially induced morphine pseudosensitization in adolescent mice

Cited by 24 publications

References 83 publications

Social influences on morphine sensitization in adolescent females

Social influences on morphine sensitization in adolescent females

Age-dependent and strain-dependent influences of morphine on mouse social investigation behavior

Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin

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