Skip to main content

Advertisement

SpringerLink
Log in

Effects of cocaine combined with a social cue on conditioned place preference and nucleus accumbens monoamines after isolation rearing in rats

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Social interaction during drug exposure can potentiate cocaine reward. Isolation rearing (ISO) during adolescence increases social interaction and may amplify this potentiation.

Objectives

The objectives of this study are to determine whether ISO alters conditioned place preference (CPP) for cocaine when combined with a social cue and to determine whether ISO alters the effects of cocaine when combined with social cue on nucleus accumbens shell (NAcS) dopamine (DA) and serotonin (5-HT).

Methods

Male and female rats were either ISO or group (GRP) reared for 4 weeks during adolescence. CPP was performed using a low dose of cocaine (2 mg/kg or saline) with or without exposure to a novel same-sex conspecific during conditioning. In vivo microdialysis was performed using the same parameters.

Results

ISO rats engaged in more social and aggressive behaviors during conditioning relative to GRP. Cocaine reduced social and aggressive behaviors in all rats. CPP was not influenced by rearing condition. Cocaine produced significant CPP, and a social cue produced CPP only in males. In contrast, the interaction of cocaine and a social cue on NAcS DA and 5-HT differed depending upon rearing condition. In isolates, cocaine-induced DA was attenuated, while cocaine plus a social cue produced potentiated DA and 5-HT.

Conclusions

Exposure to a low dose of cocaine in the presence of a social cue produced additive effects on CPP while producing synergistic effects on DA and 5-HT in the NAcS of ISO rats. The aversive effects of this compound stimulus may negate the rewarding effects in isolates.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Achterberg EJ, Trezza V, Siviy SM, Schrama L, Schoffelmeer AN, Vanderschuren LJ (2013) Amphetamine and cocaine suppress social play behavior in rats through distinct mechanisms. Psychopharmacology (Berl)

  • Auclair AL, Cathala A, Sarrazin F, Depoortere R, Piazza PV, Newman-Tancredi A, Spampinato U (2010) The central serotonin 2B receptor: a new pharmacological target to modulate the mesoaccumbens dopaminergic pathway activity. J Neurochem 114:1323–1332

    CAS  PubMed  Google Scholar 

  • Baarendse PJ, Limpens JH, Vanderschuren LJ (2013) Disrupted social development enhances the motivation for cocaine in rats. Psychopharmacology (Berl)

  • Bland ST, Twining C, Watkins LR, Maier SF (2003) Stressor controllability modulates stress-induced serotonin but not dopamine efflux in the nucleus accumbens shell. Synapse 49:206–208

    Article  CAS  PubMed  Google Scholar 

  • Bland ST, Schmid MJ, Watkins LR, Maier SF (2004) Prefrontal cortex serotonin, stress, and morphine-induced nucleus accumbens dopamine. Neuroreport 15:2637–2641

    Article  CAS  PubMed  Google Scholar 

  • Bland ST, Hutchinson MR, Maier SF, Watkins LR, Johnson KW (2009) The glial activation inhibitor AV411 reduces morphine-induced nucleus accumbens dopamine release. Brain Behav Immun 23:492–497

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Calcagnetti DJ, Schechter MD (1992) Place conditioning reveals the rewarding aspect of social interaction in juvenile rats. Physiol Behav 51:667–672

    Article  CAS  PubMed  Google Scholar 

  • Christianson JP, Paul ED, Irani M, Thompson BM, Kubala KH, Yirmiya R, Watkins LR, Maier SF (2008) The role of prior stressor controllability and the dorsal raphe nucleus in sucrose preference and social exploration. Behav Brain Res 193:87–93

    Article  PubMed Central  PubMed  Google Scholar 

  • Craige CP, Unterwald EM (2013) Serotonin (2C) receptor regulation of cocaine-induced conditioned place preference and locomotor sensitization. Behav Brain Res 238:206–210

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Der-Avakian A, Bland ST, Schmid MJ, Watkins LR, Spencer RL, Maier SF (2006) The role of glucocorticoids in the uncontrollable stress-induced potentiation of nucleus accumbens shell dopamine and conditioned place preference responses to morphine. Psychoneuroendocrinology 31:653–663

    Article  CAS  PubMed  Google Scholar 

  • Douglas LA, Varlinskaya EI, Spear LP (2004) Rewarding properties of social interactions in adolescent and adult male and female rats: impact of social versus isolate housing of subjects and partners. Dev Psychobiol 45:153–162

    Article  PubMed  Google Scholar 

  • Epstein JA, Bang H, Botvin GJ (2007) Which psychosocial factors moderate or directly affect substance use among inner-city adolescents? Addict Behav 32:700–713

    Article  PubMed  Google Scholar 

  • Ettenberg A, Geist TD (1991) Animal model for investigating the anxiogenic effects of self-administered cocaine. Psychopharmacology (Berl) 103:455–461

    Article  CAS  Google Scholar 

  • Ettenberg A, Raven MA, Danluck DA, Necessary BD (1999) Evidence for opponent-process actions of intravenous cocaine. Pharmacol Biochem Behav 64:507–512

    Article  CAS  PubMed  Google Scholar 

  • Ettenberg A, Ofer OA, Mueller CL, Waldroup S, Cohen A, Ben-Shahar O (2011) Inactivation of the dorsal raphe nucleus reduces the anxiogenic response of rats running an alley for intravenous cocaine. Pharmacol Biochem Behav 97:632–639

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ferdman N, Murmu RP, Bock J, Braun K, Leshem M (2007) Weaning age, social isolation, and gender, interact to determine adult explorative and social behavior, and dendritic and spine morphology in prefrontal cortex of rats. Behav Brain Res 180:174–182

    Article  CAS  PubMed  Google Scholar 

  • File SE, Seth P (2003) A review of 25 years of the social interaction test. Eur J Pharmacol 463:35–53

    Article  CAS  PubMed  Google Scholar 

  • Floresco SB, West AR, Ash B, Moore H, Grace AA (2003) Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmission. Nat Neurosci 6:968–973

    Article  CAS  PubMed  Google Scholar 

  • Fone KC, Porkess MV (2008) Behavioural and neurochemical effects of post-weaning social isolation in rodents-relevance to developmental neuropsychiatric disorders. Neurosci Biobehav Rev 32:1087–1102

    Article  CAS  PubMed  Google Scholar 

  • Fritz M, El Rawas R, Klement S, Kummer K, Mayr MJ, Eggart V, Salti A, Bardo MT, Saria A, Zernig G (2011) Differential effects of accumbens core vs. shell lesions in a rat concurrent conditioned place preference paradigm for cocaine vs. social interaction. PLoS One 6:e26761

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fulford AJ, Marsden CA (2007) An intact dopaminergic system is required for context-conditioned release of 5-HT in the nucleus accumbens of postweaning isolation-reared rats. Neuroscience 149:392–400

    Article  CAS  PubMed  Google Scholar 

  • Gipson CD, Beckmann JS, El-Maraghi S, Marusich JA, Bardo MT (2010) Effect of environmental enrichment on escalation of cocaine self-administration in rats. Psychopharmacology (Berl) 214:557–566

    Article  Google Scholar 

  • Green TA, Alibhai IN, Roybal CN, Winstanley CA, Theobald DE, Birnbaum SG, Graham AR, Unterberg S, Graham DL, Vialou V, Bass CE, Terwilliger EF, Bardo MT, Nestler EJ (2010) Environmental enrichment produces a behavioral phenotype mediated by low cyclic adenosine monophosphate response element binding (CREB) activity in the nucleus accumbens. Biol Psychiatry 67:28–35

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hall FS (1998) Social deprivation of neonatal, adolescent, and adult rats has distinct neurochemical and behavioral consequences. Crit Rev Neurobiol 12:129–162

    Article  CAS  PubMed  Google Scholar 

  • Hall FS, Humby T, Wilkinson LS, Robbins TW (1997) The effects of isolation-rearing on preference by rats for a novel environment. Physiol Behav 62:299–303

    Article  CAS  PubMed  Google Scholar 

  • Hall FS, Wilkinson LS, Humby T, Inglis W, Kendall DA, Marsden CA, Robbins TW (1998) Isolation rearing in rats: pre- and postsynaptic changes in striatal dopaminergic systems. Pharmacol Biochem Behav 59:859–872

    Article  CAS  PubMed  Google Scholar 

  • Hatch AM, Wiberg GS, Zawidzka Z, Cann M, Airth JM, Grice HC (1965) Isolation syndrome in the rat. Toxicol Appl Pharmacol 7:737–745

    Article  CAS  PubMed  Google Scholar 

  • Hermes G, Li N, Duman C, Duman R (2010) Post-weaning chronic social isolation produces profound behavioral dysregulation with decreases in prefrontal cortex synaptic-associated protein expression in female rats. Physiol Behav 104:354–359

    Article  PubMed Central  PubMed  Google Scholar 

  • Hicks BM, South SC, Dirago AC, Iacono WG, McGue M (2009) Environmental adversity and increasing genetic risk for externalizing disorders. Arch Gen Psychiatry 66:640–648

    Article  PubMed Central  PubMed  Google Scholar 

  • Howes SR, Dalley JW, Morrison CH, Robbins TW, Everitt BJ (2000) Leftward shift in the acquisition of cocaine self-administration in isolation-reared rats: relationship to extracellular levels of dopamine, serotonin and glutamate in the nucleus accumbens and amygdala-striatal FOS expression. Psychopharmacology (Berl) 151:55–63

    Article  CAS  Google Scholar 

  • Hurst JL, Barnard CJ, Tolladay U, Nevision CM, West CD (1999) Housing and welfare in laboratory rats: effects of cage stocking density and behavioural predictors of welfare. Anim Behav 58:563–586

    Article  PubMed  Google Scholar 

  • Johnston AL, File SE (1991) Sex differences in animal tests of anxiety. Physiol Behav 49:245–250

    Article  CAS  PubMed  Google Scholar 

  • Jones GH, Hernandez TD, Kendall DA, Marsden CA, Robbins TW (1992) Dopaminergic and serotonergic function following isolation rearing in rats: study of behavioural responses and postmortem and in vivo neurochemistry. Pharmacol Biochem Behav 43:17–35

    Article  CAS  PubMed  Google Scholar 

  • Krebs-Thomson K, Giracello D, Solis A, Geyer MA (2001) Post-weaning handling attenuates isolation-rearing induced disruptions of prepulse inhibition in rats. Behav Brain Res 120:221–224

    Article  CAS  PubMed  Google Scholar 

  • Kummer K, Klement S, Eggart V, Mayr MJ, Saria A, Zernig G (2011) Conditioned place preference for social interaction in rats: contribution of sensory components. Front Behav Neurosci 5:80

    PubMed Central  PubMed  Google Scholar 

  • Lapiz MD, Fulford A, Muchimapura S, Mason R, Parker T, Marsden CA (2003) Influence of postweaning social isolation in the rat on brain development, conditioned behavior, and neurotransmission. Neurosci Behav Physiol 33:13–29

    Article  CAS  PubMed  Google Scholar 

  • Liegeois JF, Ichikawa J, Meltzer HY (2002) 5-HT(2A) receptor antagonism potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and inhibits that in the nucleus accumbens in a dose-dependent manner. Brain Res 947:157–165

    Article  CAS  PubMed  Google Scholar 

  • Logan DE, Rose JB (2004) Gender differences in post-operative pain and patient controlled analgesia use among adolescent surgical patients. Pain 109:481–487

    Article  PubMed  Google Scholar 

  • Lukkes JL, Watt MJ, Lowry CA, Forster GL (2009) Consequences of post-weaning social isolation on anxiety behavior and related neural circuits in rodents. Front Behav Neurosci 3:18

    Article  PubMed Central  PubMed  Google Scholar 

  • McCormick CM, Mathews IZ (2009) Adolescent development, hypothalamic–pituitary–adrenal function, and programming of adult learning and memory. Prog Neuropsychopharmacol Biol Psychiatry 34:756–765

    Article  PubMed  Google Scholar 

  • Miczek KA, O’Donnell JM (1978) Intruder-evoked aggression in isolated and nonisolated mice: effects of psychomotor stimulants and L-dopa. Psychopharmacology (Berl) 57:47–55

    Article  CAS  Google Scholar 

  • Moller M, Du Preez JL, Emsley R, Harvey BH (2010) Isolation rearing-induced deficits in sensorimotor gating and social interaction in rats are related to cortico-striatal oxidative stress, and reversed by sub-chronic clozapine administration. Eur Neuropsychopharmacol 21:471–483

    Article  PubMed  Google Scholar 

  • Morutto SL, Phillips GD (1997) Isolation rearing enhances the locomotor stimulant properties of intra-perifornical sulpiride, but impairs the acquisition of a conditioned place preference. Psychopharmacology (Berl) 133:224–232

    Article  CAS  Google Scholar 

  • Navailles S, Moison D, Ryczko D, Spampinato U (2006) Region-dependent regulation of mesoaccumbens dopamine neurons in vivo by the constitutive activity of central serotonin2C receptors. J Neurochem 99:1311–1319

    Article  CAS  PubMed  Google Scholar 

  • Panksepp J (1981) The ontogeny of play in rats. Dev Psychobiol 14:327–332

    Article  CAS  PubMed  Google Scholar 

  • Panksepp J, Herman BH, Vilberg T, Bishop P, DeEskinazi FG (1980) Endogenous opioids and social behavior. Neurosci Biobehav Rev 4:473–487

    Article  CAS  PubMed  Google Scholar 

  • Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates, 6th edn. Academic Press/Elsevier

  • Phillips GD, Howes SR, Whitelaw RB, Robbins TW, Everitt BJ (1994a) Isolation rearing impairs the reinforcing efficacy of intravenous cocaine or intra-accumbens d-amphetamine: impaired response to intra-accumbens D1 and D2/D3 dopamine receptor antagonists. Psychopharmacology (Berl) 115:419–429

    Article  CAS  Google Scholar 

  • Phillips GD, Howes SR, Whitelaw RB, Wilkinson LS, Robbins TW, Everitt BJ (1994b) Isolation rearing enhances the locomotor response to cocaine and a novel environment, but impairs the intravenous self-administration of cocaine. Psychopharmacology (Berl) 115:407–418

    Article  CAS  Google Scholar 

  • Philpot RM, McQuown S, Kirstein CL (2001) Stereotaxic localization of the developing nucleus accumbens septi. Brain Res Dev Brain Res 130:149–153

    Article  CAS  PubMed  Google Scholar 

  • Rademacher DJ, Schuyler AL, Kruschel CK, Steinpreis RE (2002) Effects of cocaine and putative atypical antipsychotics on rat social behavior: an ethopharmacological study. Pharmacol Biochem Behav 73:769–778

    Article  CAS  PubMed  Google Scholar 

  • Rosa ML, Silva RC, Moura-de-Carvalho FT, Brandao ML, Guimaraes FS, Del Bel EA (2005) Routine post-weaning handling of rats prevents isolation rearing-induced deficit in prepulse inhibition. Braz J Med Biol Res 38:1691–1696

    Article  CAS  PubMed  Google Scholar 

  • Schenk S, Hunt T, Colle L, Amit Z (1983) Isolation versus grouped housing in rats: differential effects of low doses of heroin in the place preference paradigm. Life Sci 32:1129–1134

    Article  CAS  PubMed  Google Scholar 

  • Schenk S, Hunt T, Malovechko R, Robertson A, Klukowski G, Amit Z (1986) Differential effects of isolation housing on the conditioned place preference produced by cocaine and amphetamine. Pharmacol Biochem Behav 24:1793–1796

    Article  CAS  PubMed  Google Scholar 

  • Schenk S, Lacelle G, Gorman K, Amit Z (1987) Cocaine self-administration in rats influenced by environmental conditions: implications for the etiology of drug abuse. Neurosci Lett 81:227–231

    Article  CAS  PubMed  Google Scholar 

  • Sfikakis A, Galanopoulou P, Konstandi M, Tsakayannis D (1996) Stress through handling for vaginal screening, serotonin, and ACTH response to ether. Pharmacol Biochem Behav 53:965–970

    Article  CAS  PubMed  Google Scholar 

  • Skinner ML, Haggerty KP, Fleming CB, Catalano RF (2009) Predicting functional resilience among young-adult children of opiate-dependent parents. J Adolesc Health 44:283–290

    Article  PubMed Central  PubMed  Google Scholar 

  • Smith MA, Chisholm KA, Bryant PA, Greene JL, McClean JM, Stoops WW, Yancey DL (2005) Social and environmental influences on opioid sensitivity in rats: importance of an opioid’s relative efficacy at the mu-receptor. Psychopharmacology (Berl) 181:27–37

    Article  CAS  Google Scholar 

  • Smith MA, Iordanou JC, Cohen MB, Cole KT, Gergans SR, Lyle MA, Schmidt KT (2009) Effects of environmental enrichment on sensitivity to cocaine in female rats: importance of control rates of behavior. Behav Pharmacol 20:312–321

    Article  PubMed Central  PubMed  Google Scholar 

  • Spear LP (2000) The adolescent brain and age-related behavioral manifestations. Neurosci Biobehav Rev 24:417–463

    Article  CAS  PubMed  Google Scholar 

  • Stack A, Carrier N, Dietz D, Hollis F, Sorenson J, Kabbaj M (2010) Sex differences in social interaction in rats: role of the immediate-early gene zif268. Neuropsychopharmacology 35:570–580

    Article  PubMed Central  PubMed  Google Scholar 

  • Thiel KJ, Okun AC, Neisewander JL (2008) Social reward-conditioned place preference: a model revealing an interaction between cocaine and social context rewards in rats. Drug Alcohol Depend 96:202–212

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tirelli E, Laviola G, Adriani W (2003) Ontogenesis of behavioral sensitization and conditioned place preference induced by psychostimulants in laboratory rodents. Neurosci Biobehav Rev 27:163–178

    Article  PubMed  Google Scholar 

  • Trezza V, Damsteegt R, Manduca A, Petrosino S, Van Kerkhof LW, Pasterkamp RJ, Zhou Y, Campolongo P, Cuomo V, Di Marzo V, Vanderschuren LJ (2012) Endocannabinoids in amygdala and nucleus accumbens mediate social play reward in adolescent rats. J Neurosci 32:14899–14908

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tzschentke TM (2007) Measuring reward with the conditioned place preference (CPP) paradigm: update of the last decade. Addict Biol 12:227–462

    Article  CAS  PubMed  Google Scholar 

  • Vale AL, Montgomery AM (1997) Social interaction: responses to chlordiazepoxide and the loss of isolation-reared effects with paired-housing. Psychopharmacology (Berl) 133:127–132

    Article  CAS  Google Scholar 

  • Varlinskaya EI, Spear LP (2008) Social interactions in adolescent and adult Sprague–Dawley rats: impact of social deprivation and test context familiarity. Behav Brain Res 188:398–405

    Article  PubMed Central  PubMed  Google Scholar 

  • Wall VL, Fischer EK, Bland ST (2012) Isolation rearing attenuates social interaction-induced expression of immediate early gene protein products in the medial prefrontal cortex of male and female rats. Physiol Behav 107:440–450

    Article  CAS  PubMed  Google Scholar 

  • Wongwitdecha N, Marsden CA (1995) Isolation rearing prevents the reinforcing properties of amphetamine in a conditioned place preference paradigm. Eur J Pharmacol 279:99–103

    Article  CAS  PubMed  Google Scholar 

  • Wongwitdecha N, Marsden CA (1996a) Effect of social isolation on the reinforcing properties of morphine in the conditioned place preference test. Pharmacol Biochem Behav 53:531–534

    Article  CAS  PubMed  Google Scholar 

  • Wongwitdecha N, Marsden CA (1996b) Social isolation increases aggressive behaviour and alters the effects of diazepam in the rat social interaction test. Behav Brain Res 75:27–32

    Article  CAS  PubMed  Google Scholar 

  • Yajie D, Lin K, Baoming L, Lan M (2005) Enhanced cocaine self-administration in adult rats with adolescent isolation experience. Pharmacol Biochem Behav 82:673–677

    Article  Google Scholar 

  • Yorgason JT, Espana RA, Konstantopoulos JK, Weiner JL, Jones SR (2013) Enduring increases in anxiety-like behavior and rapid nucleus accumbens dopamine signaling in socially isolated rats. Eur J Neurosci 37:1022–1031

    Article  PubMed  Google Scholar 

  • Zakharova E, Miller J, Unterwald E, Wade D, Izenwasser S (2009a) Social and physical environment alter cocaine conditioned place preference and dopaminergic markers in adolescent male rats. Neuroscience 163:890–897

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zakharova E, Wade D, Izenwasser S (2009b) Sensitivity to cocaine conditioned reward depends on sex and age. Pharmacol Biochem Behav 92:131–134

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhao X, Sun L, Jia H, Meng Q, Wu S, Li N, He S (2009) Isolation rearing induces social and emotional function abnormalities and alters glutamate and neurodevelopment-related gene expression in rats. Prog Neuropsychopharmacol Biol Psychiatry 33:1173–1177

    Article  CAS  PubMed  Google Scholar 

Download references

This work was supported by NIH Grant R03DA029673. Dayton Goodell and Cassandra Hayter were supported by NIH undergraduate training grant R25NS080685.

Conflicts of interest

The authors have no conflicts of interest to report.

Author information

Authors and Affiliations

  1. Department of Psychology, University of Colorado Denver, North Classroom Building, Rm. 5002 1200 Larimer Street, Denver, CO, 80217-3364, USA

    Susan K. Grotewold, Vanessa L. Wall, Cassandra Hayter & Sondra T. Bland

  2. Department of Neuroscience, University of Colorado Denver, Denver, CO, USA

    Dayton J. Goodell

Authors
  1. Susan K. Grotewold
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vanessa L. Wall
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dayton J. Goodell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cassandra Hayter
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sondra T. Bland
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sondra T. Bland.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grotewold, S.K., Wall, V.L., Goodell, D.J. et al. Effects of cocaine combined with a social cue on conditioned place preference and nucleus accumbens monoamines after isolation rearing in rats. Psychopharmacology 231, 3041–3053 (2014). https://doi.org/10.1007/s00213-014-3470-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-014-3470-0

Keywords

Search

Navigation