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  • Addiction, Drugs
  • Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation

    818—Opioid Reinforcement, Seeking, and Reinstatement

    Wednesday, November 13, 2013, 1:00 pm - 5:00 pm

    818.08: Opiate reward in male and female prairie voles

    Location: Halls B-H

    *P. C. KEYES1, B. J. ARAGONA2;
    2Psychology, 1Univ. of Michigan, Ann Arbor, MI

    Abstract Body: A fundamental problem in addiction is the inability to stop using drugs despite adverse social consequences. Specifically, drug experience can disrupt the ability to form adaptive social bonds. Conversely, positive social bonds in drug naïve individuals can protect against the transition from casual to compulsive drug use. The neurobiology underlying this reciprocal relationship between social bonding and drug experience can been studied in the socially monogamous prairie vole, a rodent species which forms enduring pair bonds with one mating partner. Previous research has shown that amphetamine can disrupt a prairie vole’s ability to form a pair bond. Conversely, pair bonded prairie voles display resilience against amphetamine reward. Thus far, this drug-social interaction has only been studied using amphetamine. It is essential to extend this research to other drug classes, including opiates. As endogenous opioids are necessary in mediating social bonding, it is important to elucidate how opiate drugs can affect social behavior. Here, we show for the first time that non-pair bonded male and female prairie voles are susceptible to opiate reward. Using a conditioned place preference paradigm, we established a dose-response relationship of both oxycodone and morphine reward in male and female prairie voles. Additionally, we characterized the behavioral response evoked by various doses of oxycodone and morphine. These preliminary data offer a foundation for further investigation into the behavioral and neurobiological effects of opiate drugs on social bonding.

    Lay Language Summary: Work from our lab and others indicates a reciprocal relationship between the neurological and behavioral effects of drugs of abuse and social bonding. Specifically, pre-exposure to amphetamine before forming strong, positive social relationships can impair the ability to form future bonds. Conversely, intact selective social bonds can preempt the development of amphetamine-seeking behavior. Our current research aims to extend these previous findings to opiate drugs.
    Addiction is an insidious disease that consumes the lives of millions each year. Of the many negative aspects of addiction, deteriorating social relationships are prominent and highly debilitating. Indeed, drugs of abuse (e.g., alcohol, cocaine, heroin) usurp the desire to seek natural rewards, including social bonding. Fortunately, the risk of developing addiction can be allayed by pre-existing strong social bonds, such as adult monogamous relationships. Unfortunately, the converse situation is also true, in that active addicts tend to have less satisfying relationships than non-addicts, and the divorce rate is higher among addicts. It is thus essential to establish strong social bonds before drugs of abuse have the opportunity to take over. Since addicts, even after years of abstinence, have a high propensity to relapse, it seems likely that reversing the disease may not be possible. Thus, preventing the development of addiction is a prime candidate for alleviating the impact of this disease on human lives.
    Our current research examines this neuroprotection against drug reward in a rodent species called the prairie vole. Prairie voles are socially monogamous creatures that form enduring pair bonds with one mating partner. After a pair bond forms, the bonded prairie vole is not susceptible to the rewarding properties of amphetamine at a dose that is rewarding to non-pair bonded prairie voles. Our research seeks to examine whether these neuroprotective effects apply to opiate drugs as well.
    To test our hypothesis that pair bonding protects against opiate reward, we first needed to characterize the rewarding properties of opiate drugs (i.e., oxycodone and morphine) in non-bonded voles. We used a conditioned place preference procedure to do so, which indirectly measures drug-seeking behavior. We utilized an apparatus of two visually distinct chambers connected by a tube. Male and female voles were conditioned to associate one chamber’s visual cues with an injection of a certain dose of an opiate drug, and the other’s with an injection of saline. After conditioning, the animals were given access to both chambers. Animal that chose to spend significantly more time in the opiate-paired chamber had formed a “conditioned place preference”. In other words, we infer that exposure to the opiate-paired visual cues caused the animal to approach and remain in that chamber due to a conditioned association between those cues and a rewarding dose of an opiate drug.
    Using this procedure, we established a dose-response curve comparing opiate dose and the magnitude of the conditioned place preference induced. Our results indicate that, at the appropriate dose, non-pair bonded male and female prairie voles are vulnerable to opiate reward. These findings provide a foundation for further research into the effect of opiate drugs on social bonding, and vice versa. Indeed, in the future we plan to investigate the rewarding effects (or lack thereof) of opiate drugs in pair bonded voles at doses that are rewarding to non-pair bonded voles. Additionally, we will investigate what neurobiological mechanisms common to both drug reward and pair bonding mediate these effects. These preclinical studies will elucidate behavioral interventions and their neurobiological underpinnings that can prevent the debilitating social costs of addiction before the disease can take hold, and thus emphasize a key role for prevention in the treatment of addiction