Conditioned place preference induced by social play behavior: Parametrics, extinction, reinstatement and disruption by methylphenidate

https://doi.org/10.1016/j.euroneuro.2009.03.006Get rights and content

Abstract

In this study, we investigated behavioral factors underlying conditioned place preference (CPP) induced by social interaction in adolescent rats. We found that the magnitude of socially-induced CPP depended on the social motivation of the animals and on the amount of training. After extinction, socially-induced CPP could be reinstated by a single reconditioning session. Treatment with methylphenidate, which disrupts social play behavior in adolescent rats, but not social exploratory behavior, prevented the development of socially-induced CPP. Interestingly, methylphenidate by itself induced CPP. These data demonstrate that: 1. social interaction is rewarding in adolescent rats; 2. appetitive and mnemonic factors influence the development of socially-induced CPP; 3. comparable to drug-induced CPP, socially-induced CPP can be extinguished and reinstated; 4. social play is likely to be the most rewarding aspect of social interaction in adolescent rats; 5. social context influences the subjective effects of methylphenidate.

Introduction

Natural rewards are linked with behaviors that are essential for survival of the individual, group, or species. Feeding, drinking, and sexual behavior are such pleasurable activities that can function as reinforcers. Alongside these generally known natural reinforcers, social interactions are also known to be pleasurable, and it is quite clear that social interactions serve to acquire and maintain important intra-species relationships. In most mammals, interactions with peers are particularly abundant during adolescence, and it is thought that peer–peer interactions during adolescence are of major importance for social and cognitive development (Fagen, 1981, Vanderschuren et al., 1997, Nelson et al., 2005). Early laboratory experiments have shown that social interactions can function as reinforcers in young primates (Falk, 1958, Mason et al., 1963), and later work demonstrated that the opportunity to engage in social play was a reinforcer for maze learning in adolescent rats (Humphreys and Einon, 1981, Normansell and Panksepp, 1990). Place conditioning, where an animal comes to approach previously neutral environmental cues after these have been repeatedly paired with a pleasurable drug or event, can be used to investigate the neural and psychological basis of reward (Schechter and Calcagnetti, 1993, Bardo and Bevins, 2000, Tzschentke, 1998, Tzschentke, 2007). Indeed, social play behavior in adolescent rats has been shown to induce conditioned place preference (CPP; Calcagnetti and Schechter, 1992, Crowder and Hutto, 1992, Van den Berg et al., 1999, Douglas et al., 2004, Thiel et al., 2008, Thiel et al., 2009).

Although social play behavior is known to induce CPP, the exact underlying behavioral mechanisms remain unclear. Therefore, the present study aimed to identify appetitive and mnemonic factors underlying socially-induced CPP in adolescent rats. In addition, we aimed to investigate whether it was social play behavior specifically, or social interaction in general, that caused socially-induced CPP in adolescent rats. Thus, the first three experiments investigated how social motivation influences the development of socially-induced CPP, by comparing groups of rats isolated for different periods before place conditioning, as it is known that the amount of social play behavior displayed by adolescent rats is a function of the duration of the preceding social isolation period (Niesink and Van Ree, 1989, Vanderschuren et al., 1995a, Vanderschuren et al., 2008). These experiments provide important information about how changes in social motivation influence socially-induced CPP. Also, by varying the number and duration of conditioning sessions, we aimed to understand whether the amount of training influences the development of CPP. In addition, we tested whether socially-induced CPP was subject to extinction. In general, CPP extinguishes with repeated exposure to the conditioning environment without the primary pleasurable stimulus, but several studies have shown that CPP can be remarkably persistent (e.g. Mueller et al., 2002, Mueller and Stewart, 2000), perhaps demonstrating that the reward-associated cues had become attractive stimuli by themselves (see Di Ciano and Everitt, 2004). In recent years, extinction/reinstatement procedures have been successfully applied to place conditioning experiments, showing that expression of drug-induced CPP can be reinstated by a single drug re-exposure or by stress (for review see Tzschentke, 2007). Therefore, we tested whether a reconditioning session could reinstate extinguished socially-induced CPP.

In the second part of the study, we addressed the notion (Humphreys and Einon, 1981, Pellis and McKenna, 1995) that play is the most positive, rewarding aspect of the social repertoire of adolescent rats. To that aim, we treated the animals with methylphenidate to interfere with the expression of social play. We have recently shown that methylphenidate suppresses social play behavior in adolescent rats. Methylphenidate suppressed both play solicitation and responsiveness to play solicitation, without affecting social exploratory behavior. However, vehicle-treated animals still solicited play from methylphenidate-treated test partners (Vanderschuren et al., 2008). Thus, by treating either the test animal, the stimulus animal, or both with methylphenidate, we investigated the extent to which play solicitation, being solicited, social interaction with a non-playful partner and full expression of social play behavior contribute to the development of socially-induced CPP. Since social behaviors related and unrelated to play have different ontogenetic profiles and are also differently affected by drug treatments (Vanderschuren et al., 1997), understanding their relative contribution to the positive subjective properties of social interaction will help to understand the brain mechanisms involved in the regulation of social reward.

Section snippets

Animals

Male Wistar rats (Charles River, Sulzfeld, Germany) arrived in our animal facility at 21 days of age and were housed in groups of three in 40 × 26 × 20 (l × w × h) Macrolon cages under controlled conditions (i.e. temperature 20–21 °C, 60–65% relative humidity and 12/12 h light cycle with lights on at 7.00 a.m.). Upon arrival, the animals were allowed at least five days of acclimatization to our facility and they were handled for 3 days before the start of the experiments. Food and water were available

Discussion

The present study had the following aims: 1. to understand how motivational aspects of social interaction in adolescent rats contribute to the development of socially-induced CPP. 2. to understand how the amount of training influences socially-induced CPP and whether socially-induced CPP is susceptible to extinction and reinstatement, like drug-induced CPP. 3. to test the hypothesis that conditioning with play-unresponsive partners would prevent the development of socially-induced CPP, and to

Role of the funding source

Funding for this study was provided by National Institute on Drug Abuse Grant R01 DA022628-01 (L.J.M.J.V.), and a fellowship from the Fondazione Enrico ed Enrica Sovena, Rome (V.T.). This research was performed within the framework of project T5-107 of the Dutch Top Institute Pharma. The National Institute on Drug Abuse, the Fondazione Enrico ed Enrica Sovena and the Dutch Top Institute Pharma had no further role in study design; in the collection, analysis and interpretation of data; in the

Contributors

Authors Viviana Trezza and Louk J.M.J. Vanderschuren designed the study. Authors Viviana Trezza and Ruth Damsteegt performed the experiments and analysed the data. Authors Viviana Trezza and Louk J.M.J. Vanderschuren wrote the manuscript. All authors contributed to and have approved the final manuscript.

Conflict of interest

The authors declare that they have no conflicts of interest.

Acknowledgements

Supported by National Institute on Drug Abuse Grant R01 DA022628-01 (L.J.M.J.V.). This research was performed within the framework of project T5-107 of the Dutch Top Institute Pharma. V. Trezza was a visiting scientist from the Dept. of Human Physiology and Pharmacology, University of Rome ‘Sapienza’, Rome, Italy, supported by a fellowship from “Fondazione Enrico ed Enrica Sovena”, Rome.

References (44)

  • NiesinkR.J.M. et al.

    Involvement of opioid and dopaminergic systems in isolation-induced pinning and social grooming of young rats

    Neuropharmacology

    (1989)
  • PankseppJ. et al.

    Social deprivation and play in rats

    Behav. Neural Biol.

    (1980)
  • PankseppJ. et al.

    50-kHz chirping (laughter?) in response to conditioned and unconditioned tickle-induced reward in rats: effects of social housing and genetic variables

    Behav. Brain Res.

    (2000)
  • PankseppJ. et al.

    The psychobiology of play: theoretical and methodological perspectives

    Neurosci. Biobehav. Rev.

    (1984)
  • PellisS.M. et al.

    Intrinsic and extrinsic influences on play fighting in rats: effects of dominance, partner's playfulness, temperament and neonatal exposure to testosterone propionate

    Behav. Brain Res.

    (1992)
  • PellisS.M. et al.

    What do rats find rewarding in play fighting—an analysis using drug-induced non-playful partners

    Behav. Brain Res.

    (1995)
  • PerksS.M. et al.

    Reinforcer revaluation and conditioned place preference

    Physiol. Behav.

    (1997)
  • SchechterM.D. et al.

    Trends in place preference conditioning with a cross-indexed bibliography: 1957–1991

    Neurosci. Biobehav. Rev.

    (1993)
  • ThielK.J. et al.

    Social reward-conditioned place preference: a model revealing an interaction between cocaine and social context rewards in rats

    Drug Alcohol Depend.

    (2008)
  • ThorD.H. et al.

    Social play in juvenile rats: a decade of methodological and experimental research

    Neurosci. Biobehav. Rev.

    (1984)
  • TrezzaV. et al.

    Cannabinoid and opioid modulation of social play behavior in adolescent rats: differential behavioral mechanisms

    Eur. Neuropsychopharmacol.

    (2008)
  • TzschentkeT.M.

    Measuring reward with the conditioned place preference paradigm: a comprehensive review of drug effects, recent progress and new issues

    Prog. Neurobiol.

    (1998)
  • Cited by (94)

    View all citing articles on Scopus
    View full text