Adolescent Opiate Exposure in the Female Rat Induces Subtle Alterations in Maternal Care and Transgenerational Effects on Play Behavior

Department of Biomedical Science, Cummings School of Veterinary Medicine, Tufts University North Grafton, MA, USA.
Frontiers in Psychiatry 06/2011; 2:29. DOI: 10.3389/fpsyt.2011.00029
Source: PubMed


The non-medical use of prescription opiates, such as Vicodin(®) and MSContin(®), has increased dramatically over the past decade. Of particular concern is the rising popularity of these drugs in adolescent female populations. Use during this critical developmental period could have significant long-term consequences for both the female user as well as potential effects on her future offspring. To address this issue, we have begun modeling adolescent opiate exposure in female rats and have observed significant transgenerational effects despite the fact that all drugs are withdrawn several weeks prior to pregnancy. The purpose of the current set of studies was to determine whether adolescent morphine exposure modifies postpartum care. In addition, we also examined juvenile play behavior in both male and female offspring. The choice of the social play paradigm was based on previous findings demonstrating effects of both postpartum care and opioid activity on play behavior. The findings revealed subtle modifications in the maternal behavior of adolescent morphine-exposed females, primarily related to the amount of time females' spend nursing and in non-nursing contact with their young. In addition, male offspring of adolescent morphine-exposed mothers (MOR-F1) demonstrate decreased rough and tumble play behaviors, with no significant differences in general social behaviors (i.e., social grooming and social exploration). Moreover, there was a tendency toward increased rough and tumble play in MOR-F1 females, demonstrating the sex-specific nature of these effects. Given the importance of the postpartum environment on neurodevelopment, it is possible that modifications in maternal-offspring interactions, related to a history of adolescent opiate exposure, plays a role in the observed transgenerational effects. Overall, these studies indicate that the long-term consequences of adolescent opiate exposure can impact both the female and her future offspring.

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Available from: Elizabeth M Byrnes
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    • "Previous work with this model has shown that there are alterations in various aspects of both behavior and physiology in the offspring. For example, it was shown that adult offspring from females exposed to morphine during adolescence demonstrate increased sensitivity to the analgesic properties of morphine, develop tolerance more rapidly, have alterations in play behavior, and dopamine D2 receptor sensitivity (Byrnes et al., 2011, 2013; Johnson et al., 2011; Vassoler et al., 2014b). However, it is unclear if there are changes in the reward system in response to morphine. "
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    ABSTRACT: Prescription opiate use and abuse has increased dramatically over the past two decades, including increased use in adolescent populations. Recently, it has been proposed that use during this critical period may affect future offspring even when use is discontinued prior to conception. Here, we utilize a rodent model to examine the effects of adolescent morphine exposure on the reward functioning of the offspring. Female Sprague Dawley rats were administered morphine for 10 days during early adolescence (post-natal day 30-39) using an escalating dosing regimen. Animals then remained drug free until adulthood at which point they were mated with naïve males. Adult offspring (F1 animals) were tested for their response to morphine-induced (0, 1, 2.5, 5, and 10 mg/kg, s.c.) conditioned place preference (CPP) and context-independent morphine-induced sensitization. Naïve littermates were used to examine mu opiate receptor expression in the nucleus accumbens and ventral tegmental area. Results indicate that F1 females whose mothers were exposed to morphine during adolescence (Mor-F1) demonstrate significantly enhanced CPP to the lowest doses of morphine compared with Sal-F1 females. There were no differences in context-independent sensitization between maternal treatment groups. Protein expression analysis showed significantly increased levels of accumbal mu opiate receptor in Mor-F1 offspring and decreased levels in the VTA. Taken together, these findings demonstrate a shift in the dose response curve with regard to the rewarding effects of morphine in Mor-F1 females which may in part be due to altered mu opiate receptor expression in the nucleus accumbens and VTA.
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    • "The gestational period, however, is the most vulnerable developmental stage for the damaging effects of some drugs. Many studies have reported irreversible changes in social behaviour during adolescence and adulthood after prenatal exposure to EtOH (Lawrence et al., 2008; Hamilton et al., 2010, 2014), cocaine (Wood et al., 1994, 1995; Johns et al., 1998; Estellés et al., 2005; Magalhães et al., 2006), cannabinoids (O'Shea et al., 2006; Newsom and Kelly, 2008) and opioids (Hol et al., 1996; Niesink et al., 1996; Johnson et al., 2011). "
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    ABSTRACT: Social behaviour is disturbed in many substance abuse and psychiatric disorders. Given the consensus that social behaviours of lower mammals may help to understand some human emotional reactions, the aim of the present work was to provide an up-to-date review of studies on the changes in social behaviour induced by drugs of abuse. Various animal models have been used to study the relationship between drugs of abuse and social behaviour. Herein, we describe the effects of different substances of abuse on the three most commonly used animal models of social behaviour: the social play test, the social interaction test and the resident-intruder paradigm. The first is the most widely used test to assess adolescent behaviour in rodents, the second is generally used to evaluate a wide repertoire of behaviours in adulthood and the latter is specific to aggressive behaviour. Throughout the review we will explore the most relevant studies carried out to date to evaluate the effects of alcohol, cocaine, opioids, 3,4-methylenedioxymethamphetamine (MDMA), cannabinoids, nicotine and other drugs of abuse on these three paradigms, taking into account the influence of different variables, such as social history, age and type of exposure. Drugs of diverse pharmacological classes induce alterations in social behaviour, although they can be contrasting depending on several factors (drug, individual differences and environmental conditions). Ethanol and nicotine increase social interaction at low doses but reduce it at high doses. Psychostimulants, MDMA and cannabinoids reduce social interaction, whereas opiates increase it. Ethanol and psychostimulants enhance aggression, whereas MDMA, opiates, cannabinoids and nicotine reduce it. Prenatal drug exposure alters social behaviour, whereas drug withdrawal decreases sociability and enhances aggression. As a whole, this evidence has improved our understanding of the social dimension of drug addiction.
    No preview · Article · Sep 2015 · Behavioural pharmacology
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    • "Compared to the control juveniles, the socially stressed animals displayed consistently lower levels of social investigation . These data support previous work in rodents (Champagne and Meaney, 2007; Johnson et al., 2011; Meaney, 2001) and humans (Champagne, 2008; Matthews and Phillips, 2012; Pawlby et al., 2008; Plant et al., 2013; Ricks, 1985) on the transgenerational transmission of social behavior. In humans, the offspring of depressed mothers often suffer from mental health disorders that involve deficits in social behavior, such as infant social engagement and depression and anxiety (Burk et al., 2008; Feldman et al., 2009). "
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    ABSTRACT: Social stressors such as depressed maternal care and family conflict are robust challenges which can have long-term physiological and behavioral effects on offspring and future generations. The current study investigates the multigenerational effects of an ethologically relevant chronic social stress on the behavior and endocrinology of juvenile and adult rats. Exposure to chronic social stress during lactation impairs maternal care in F0 lactating dams and the maternal care of the F1 offspring of those stressed F0 dams. The overall hypothesis was that the male and female F2 offspring of stressed F1 dams would display decreased social behavior as both juveniles and adults and that these behavioral effects would be accompanied by changes in plasma corticosterone, prolactin, and oxytocin. Both the female and male F2 offspring of dams exposed to chronic social stress displayed decreased social behavior as juveniles and adults, and these behavioral effects were accompanied by decreases in basal concentrations of corticosterone in both sexes, as well as elevated juvenile oxytocin and decreased adult prolactin in the female offspring. The data support the conclusion that social stress has multigenerational effects on the social behavior of the female and male offspring which are mediated by changes in the hypothalamic-pituitary-adrenal axis and hypothalamic-pituitary-gonadal axes. Social stress models are valuable resources in the study of the multigenerational effects of stress on the behavioral endocrinology of disorders such as depression, anxiety, autism, and other disorders involving disrupted social behavior.
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