Concurrent choice for social interaction and amphetamine using conditioned place preference in rats: Effects of age and housing condition

https://doi.org/10.1016/j.drugalcdep.2013.02.024Get rights and content

Abstract

Background

Social interaction can serve as a natural reward that attenuates drug reward in rats; however, it is unknown if age or housing conditions alter the choice between social interaction and drug.

Methods

Individually- and pair-housed adolescent and adult male rats were tested using conditioned place preference (CPP) in separate experiments in which: (1) social interaction was conditioned against no social interaction; (2) amphetamine (AMPH; 1 mg/kg, s.c.) was conditioned against saline; or (3) social interaction was conditioned against AMPH.

Results

Social interaction CPP was obtained only in individually-housed adolescents, whereas AMPH CPP was obtained in both individually-housed adolescents and adults; however, the effect of AMPH was not statistically significant in pair-housed adults. When allowed to choose concurrently between compartments paired with either social interaction or AMPH, individually-housed adolescents preferred the compartment paired with social interaction, whereas pair-housed adolescents preferred the compartment paired with AMPH. Regardless of housing condition, adults showed a similar preference for the compartments paired with either social interaction or AMPH.

Conclusions

Although some caution is needed in interpreting cross-experiment comparisons, the overall results suggest that individually-housed adolescents were most sensitive to the rewarding effect of social interaction, and this hypersensitivity to social reward effectively competed with AMPH reward.

Introduction

The relationship between social context and drug abuse is complex. During development, peer influences contribute to experimental drug use (Allen et al., 2003, Bahr et al., 2005). In preclinical work, rats exposed to a conspecific treated with ethanol drink more ethanol relative to rats exposed to a conspecific treated with water (Hunt et al., 2001). Rats also self-administer more d-amphetamine (AMPH) when given visual access to a conspecific relative to when they are alone (Gipson et al., 2011). Furthermore, rats self-administer more cocaine in the presence of a conspecific performing the same task (Smith, 2012). Although social influences have been linked to experimental drug use, individuals with substance use disorders often decrease social interactions and spend less time with their peers (American Psychiatric Association, 1994). It is not clear to what extent the social isolation precedes or results from substance abuse.

The conditioned place preference (CPP) paradigm can assess how social interactions modulate drug reward. With CPP, animals learn to associate contextual cues with an appetitive stimulus (e.g., food, social interaction, drugs of abuse; see Bardo and Bevins, 2000, Tzschentke, 2007 for reviews on CPP). During conditioning, the previously neutral environmental cues come to act as conditioned stimuli that then elicit approach to the environment previously paired with the appetitive stimulus. Relative to rats that receive either social interaction or marginally rewarding doses of a stimulant drug alone, rats that receive simultaneous social interaction and marginal doses develop greater CPP (Thiel et al., 2008, Thiel et al., 2009). Recently, the CPP paradigm has been used to determine the relative rewarding effects of social interaction versus cocaine. For example, when social interaction and cocaine are conditioned against each other in different environments, rats show reduced CPP to both the social- and cocaine-associated environments compared to either social- or cocaine-associated environments conditioned alone (Fritz et al., 2011).

Despite the evidence that a context paired with social interaction can reduce drug-induced CPP (Fritz et al., 2011), that study was limited to adult rats housed in individual cages. Evidence indicates that adolescent rats are more sensitive than adults to the stimulant locomotor effects of cocaine (Badanich et al., 2008, Catlow and Kirstein, 2005; but see Laviola et al., 1995), and adults show greater locomotor activity to AMPH when group-housed compared to individually-housed (Gill et al., 2012, Wang et al., 2010). In addition, social interaction and drug CPP are modulated by age and housing condition. For example, adolescents show social interaction CPP regardless of housing condition, whereas adults show social interaction CPP only when isolated (Douglas et al., 2004). Age differences are also observed with drug-induced CPP, although results are somewhat mixed. Some reports show that, relative to adult rats, adolescents develop cocaine CPP at lower doses (Badanich et al., 2006, Zakharova et al., 2009a; but see Adriani and Laviola, 2003, Campbell et al., 2000) and acquire methamphetamine CPP at a faster rate (Zakharova et al., 2009a). Housing conditions also modulate drug-induced CPP in adults, as cocaine CPP is obtained in group-housed rats, but not in individually-housed rats (Schenk et al., 1986). Similarly, rats housed in an enriched condition with social partners are more sensitive than individually-housed rats to AMPH CPP tested during adulthood (Bowling and Bardo, 1994).

The present experiments sought to further validate the use of the concurrent choice CPP paradigm in which the rewarding value of different reinforcers (social interaction vs. AMPH) are conditioned against one another (Fritz et al., 2011). Although previous research has demonstrated age and housing condition effects in social interaction and drug-induced CPP, studies have not directly measured whether age or housing condition alter social interaction versus AMPH CPP. Thus, the primary goal of the present experiments was to determine if social interaction and AMPH CPP are modulated by age (adolescent vs. adult) and housing condition (individual vs. paired). In Experiment 1, adolescent and adult rats were tested for social interaction reward by receiving access to an unfamiliar sex- and weight-matched partner in one compartment and received no partner in the alternate compartment. In Experiment 2, rats were tested for drug reward by receiving AMPH (1 mg/kg) in a one compartment and saline in the alternate compartment; the dose of AMPH was selected based on previous literature indicating that it produces robust CPP (Bardo et al., 1995). AMPH-induced locomotor activity was also measured in this experiment to confirm that the AMPH dose selected produced hyperactivity across conditioning sessions. In Experiment 3, rats were tested for concurrent choice between social interaction and AMPH reward by receiving social interaction in one compartment and AMPH in the alternate compartment.

Section snippets

Animals

Male Sprague Dawley rats (Harlan Industries, Indianapolis, IN, USA) were used. Rats arrived at either postnatal day (PND) 21 or PND 60. Adolescent and adult rats were housed either individually or in pairs immediately upon delivery to the laboratory. Rats were housed in a temperature- and humidity-controlled colony room that was maintained on a light–dark cycle in which lights were on from 6:00 a.m. to 6:00 p.m. Rats were allowed to acclimate to the colony for 7 days before the start of the

Experiment 1: social-induced CPP

In Experiment 1, a 2 × 2 ANOVA revealed a main effect of age (F(1, 19) = 9.29, p < .01), with overall preference ratios being higher in adolescents than in adults. Although the overall ANOVA found no age × housing interaction, one-sample t tests revealed that individually-housed adolescent rats developed social interaction CPP (t(4) = 9.48, p < .01; Fig. 1, left panel), whereas social interaction CPP was not observed in pair-housed adolescents (Fig. 1, left panel) or in either individually- or pair-housed

Discussion

There were three main findings in the current experiments. First, social interaction CPP was obtained only in individually-housed adolescents. Second, AMPH CPP was observed in both adolescents and adults, although AMPH CPP was not statistically significant among pair-housed adults. Third, when given access to a compartment paired with either social interaction or AMPH, individually-housed adolescents preferred the social interaction compartment, whereas pair-housed adolescents preferred the

Role of funding source

This research was funded by NIH grants P50 DA05312, R01 DA12964 and T32 DA016176. The NIH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.

Contributors

All authors have contributed to and approved the final manuscript. Joshua Beckmann, Andrew Meyer, and Justin Yates designed the experiments. Justin Yates conducted the experiments, analyzed the data, and prepared the manuscript. Michael Bardo, as PI on the project, participated in study design and manuscript preparation.

Conflict of interest

All authors declare that they have no conflicts of interest.

Acknowledgements

The authors would like to thank Mr. Travis McCuddy, Mrs. Emily Denehy, and Mrs. Kristin Howell for technical assistance. We also thank Drs. Gerald Zernig and Janet Neisewander for discussions on social CPP.

References (45)

  • P. Leone et al.

    Blockade of D-1 receptors by SCH 23390 antagonizes morphine and amphetamine-induced place preference conditioning

    Eur. J. Pharmacol.

    (1987)
  • N.A. Peartree et al.

    Limited physical contact through a mesh barrier is sufficient for social reward-conditioned place preference in adolescent male rats

    Physiol. Behav.

    (2012)
  • S.M. Perks et al.

    Reinforcer revaluation and conditioned place preference

    Physiol. Behav.

    (1997)
  • H.A. Robertson

    Cerebral decortication reverses the effect of amphetamine on striatal D2 dopamine binding site density

    Neurosci. Lett.

    (1986)
  • S. Schenk et al.

    Isolation versus grouped housing in rats: differential effects of low doses of heroin in the place preference paradigm

    Life Sci.

    (1983)
  • S. Schenk et al.

    Differential effects of isolation housing on the conditioned place preference produced by cocaine and amphetamine

    Pharmacol. Biochem. Behav.

    (1986)
  • L.P. Spear

    The adolescent brain and age-related behavioral manifestations

    Neurosci. Biobehav. Rev.

    (2000)
  • C. Spyraki et al.

    Dopaminergic substrates of amphetamine-induced place preference conditioning

    Brain Res.

    (1982)
  • K.J. Thiel et al.

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

    Drug Alcohol Depend.

    (2008)
  • L. Thorn et al.

    Evidence to suggest that agonist modulation of hyperlocomotion is via post-synaptic dopamine D2 or D3 receptors

    Neuropharmacol

    (1997)
  • V. Trezza et al.

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

    Eur. Neuropsychopharmacology

    (2009)
  • C.L. Van den Berg et al.

    Isolation changes the incentive value of sucrose and social behaviour in juvenile and adult rats

    Behav. Brain Res.

    (1999)
  • Cited by (0)

    View full text