Skip to main content
Log in

Differential sensitivity to amphetamine’s effect on open field behavior of psychosocially stressed male rats

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

Abstract

Rationale

Studies of socially housed rodents have provided significant information regarding the mechanisms of stress and of stress-related disorders.

Objective

Since psychosocial stress is known to alter the functional activity of dopaminergic system, we employed amphetamine (AMP) to evaluate the involvement dopamine in mediating the behavioral consequences of psychosocial stress.

Methods

Male rats housed two per cage were designated as dominant (DOM) or subdominant (Sdom) based on initial evaluations of agonistic behaviors and body weight changes. Diad-housed rats and a group of single-housed (SiH) rats were tested in an open field after injections of saline or amphetamine (0.9 or 2.7 mg/kg IP) prior to and again while diad-housing.

Results

Compared to future DOM rats, saline-injected future Sdom rats entered the open field center less frequently, spent less time in rearing behavior and groomed less. At the pre-diad test AMP treatment elevated locomotor activity of all rats, while stimulation of center entries was more marked in future DOM rats. At the diad test, AMP’s locomotor stimulant effect was evident in all experimental groups with DOM rats showing higher effects compared to Sdom and SiH rats. Amphetamine’s stimulation of center entries in DOM rats was similar to the pre-diad test, but it was diminished in Sdom rats, while stimulation of rearing behavior was most evident in diad-housed rats.

Conclusion

The dopaminergic system modulates the psychosocial stress-induced differences in explorative and emotional behaviors. Furthermore, behavioral traits like frequency of grooming behavior and of center entries were predictive of future hierarchical status.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Ahmed SH, Stinus L, Le Moal M, Cador M (1995) Social deprivation enhances the vulnerability of male Wistar rats to stressor- and amphetamine-induced behavioral sensitization. Psychopharmacology (Berl) 117:116–124

    Article  CAS  Google Scholar 

  • Anstrom KK, Miczek KA, Budygin EA (2009) Increased phasic dopamine signaling in the mesolimbic pathway during social defeat in rats. Neuroscience 161:3–12

    Article  PubMed  CAS  Google Scholar 

  • Antoniou K, Kafetzopoulos E, Papadopoulou-Daifoti Z, Hyphantis T, Marselos M (1998) D-amphetamine, cocaine and caffeine: a comparative study of acute effects on locomotor activity and behavioural patterns in rats. Neurosci Biobehav Rev 23:189–196

    Article  PubMed  CAS  Google Scholar 

  • Araujo NP, Fukushiro DF, Cunha JL, Levin R, Chinen CC, Carvalho RC, Ribeiro IC, Gomes DC, Abilio VC, Silva RH, Ribeiro Rde A, Frussa-Filho R (2006) Drug-induced home cage conspecifics’ behavior can potentiate behavioral sensitization in mice. Pharmacol Biocehm Behav 84:142–147

    Article  CAS  Google Scholar 

  • Biała G, Kruk M (2007) Amphetamine-induced anxiety-related behavior in animal models. Pharmacol Rep 59:636–644

    PubMed  Google Scholar 

  • Björkqvist K (2001) Social defeat as a stressor in humans. Physiol Behav 73:435–442

    Article  PubMed  Google Scholar 

  • Blakley G, Pohorecky LA (2006) Psychosocial stress alters ethanol’s effect on open field behaviors. Pharmacol Biochem Behav 84:51–61

    Article  PubMed  CAS  Google Scholar 

  • Blanchard DC, Spencer RL, Weiss SM, Blanchard RJ, McEwen B, Sakai RR (1995) Visible burrow system as a model of chronic social stress: behavioral and neuroendocrine correlates. Psychoneuroendocrinology 20:117–134

    Article  PubMed  CAS  Google Scholar 

  • Blanchard RJ, Hebert MA, Ferrari PF, Palanza P, Figueira R, Blanchard DC, Parmigiani S (1998) Defensive behaviors in wild and laboratory (Swiss) mice: the mouse defense test battery. Physiol Behav 65:201–209

    Article  PubMed  CAS  Google Scholar 

  • Blanchard RJ, Yudko E, Dulloog L, Blanchard DC (2001) Defense changes in stress nonresponsive subordinate males in a visible burrow system. Physiol Behav 72:635–642

    Article  PubMed  CAS  Google Scholar 

  • Burke AR, Renner KJ, Forster GL, Watt MJ (2010) Adolescent social defeat alters neural, endocrine and behavioral responses to amphetamine in adult male rats. Brain Res 1352:147–56

    Google Scholar 

  • Coco ML, Weiss JM (2005) Neural substrates of coping behavior in the rat: possible importance of mesocorticolimbic dopamine system. Behav Neurosci 119:429–445

    Article  PubMed  CAS  Google Scholar 

  • Covington HE 3rd, Miczek KA (2001) Repeated social-defeat stress, cocaine or morphine. Effects on behavioral sensitization and intravenous cocaine self-administration "binges". Psychopharmacology (Berl) 158:388–398

    Article  CAS  Google Scholar 

  • Covington HE 3rd, Miczek KA (2005) Intense cocaine self-administration after episodic social defeat stress, but not after aggressive behavior: dissociation from corticosterone activation. Psychopharmacology (Berl) 183(3):331–340

    Article  CAS  Google Scholar 

  • Dai H, Krost M, Carey RJ (1996) A new methodological approach to the study of habituation: the use of positive and negative behavioral indices of habituation. J Neurosci Methods 62:169–174

    Article  Google Scholar 

  • Davis JF, Krause EG, Melhorn SJ, Sakai RR, Benoit SC (2009) Dominant rats are natural risk takers and display increased motivation for food reward. Neuroscience 162:23–30

    Article  PubMed  CAS  Google Scholar 

  • de Jong JG, van der Vegt BJ, Buwalda B, Koolhaas JM (2005) Social environment determines the long-term effects of social defeat. Physiol Behav 84:87–95

    Article  PubMed  Google Scholar 

  • del Pozo F, DeFeudis FV, Jimenez JM (1978) Motilities of isolated and aggregated mice; a difference in ultradian rhythmicity. Experientia 38:1302–1304

    Article  Google Scholar 

  • Deroche V, Piazza PV, Maccari S, Le Moal M, Simon H (1992) Repeated corticosterone administration sensitizes the locomotor response to amphetamine. Brain Res 584:309–313

    Article  PubMed  CAS  Google Scholar 

  • Ducottet C, Aubert A, Belzung C (2004) Susceptibility to subchronic unpredictable stress is related to individual reactivity to threat stimuli in mice. Behav Brain Res 155:291–299

    Article  PubMed  CAS  Google Scholar 

  • Duncan EA, Tamashiro KL, Nguyen MM, Gardner SR, Woods SC, Sakai RR (2006) The impact of moderate daily alcohol consumption on aggression and the formation of dominance hierarchies in rats. Psychopharmacology (Berl) 189:83–94

    Article  CAS  Google Scholar 

  • Ebner K, Wotjak CT, Landgraf R, Engelmann M (2005) Neuroendocrine and behavioral response to social confrontation: residents versus intruders, active versus passive coping styles. Horm Behav 47:14–21

    Article  PubMed  CAS  Google Scholar 

  • Ferrari PF, Palanza P, Parmigiani S, Rodgers RJ (1998) Interindividual variability in Swiss male mice: relationship between social factors, aggression, and anxiety. Physiol Behav 63:821–827

    Article  PubMed  CAS  Google Scholar 

  • Ferrari PF, van Erp AM, Tornatzky W, Miczek KA (2003) Accumbal dopamine and serotonin in anticipation of the next aggressive episode in rats. Eur J Neurosci 17:371–378

    Article  PubMed  CAS  Google Scholar 

  • Gariépy JL, Rodriguiz RM, Jones BC (2002) Handling, genetic and housing effects on the mouse stress system, dopamine function, and behavior. Pharmacol Biochem Behav 73:7–17

    Article  PubMed  Google Scholar 

  • Gaytan O, Swann AC, Dafny N (1996) Effects of amphetamine at the beginning of the light cycle on multiple indices of motor activity in the rat. Eur J Pharmacol 300:1–8

    Article  PubMed  CAS  Google Scholar 

  • Gust DA, Gordon TP, Wilson ME, Ahmed-Ansari A, Brodie AT, McLure HM (1991) Formation of a new social group of unfamiliar female rhesus monkeys affects the immune and pituitary adrenocortical systems. Brain Behav Immun 5:296–307

    Article  PubMed  CAS  Google Scholar 

  • Hall FS, Humby T, Wilkinson LS, Robbins TW (1997) The effects of isolation-rearing of rats on behavioural responses to food and environmental novelty. Physiol Behav 62:281–290

    Article  PubMed  CAS  Google Scholar 

  • Haller J, Kiem DT, Makara GB (1996) The physiology of social conflict in rats: what is particularly stressful? Behav Neurosci 110:353–359

    Article  PubMed  CAS  Google Scholar 

  • Heinrichs SC, Pich EM, Miczek KA, Britton KT, Koob GF (1992) Corticotropin-releasing factor antagonist reduces emotionality in socially defeated rats via direct neurotropic action. Brain Res 581:190–197

    Article  PubMed  CAS  Google Scholar 

  • Homayoun H, Moghaddam B (2006) Progression of cellular adaptations in medial prefrontal and orbitofrontal cortex in response to repeated amphetamine. J Neurosci 26:8025–8039

    Article  PubMed  CAS  Google Scholar 

  • Isovich E, Mijnster MJ, Flügge G, Fuchs E (2000) Chronic psychosocial stress reduces the density of dopamine transporters. Eur J Neurosci 12:1071–1078

    Article  PubMed  CAS  Google Scholar 

  • Kalivas PW, Stewart J (1991) Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity. Brain Res Brain Res Rev 16:223–244

    Article  PubMed  CAS  Google Scholar 

  • Kalivas PW, Duffy P, Latimer LG (1987) Neurochemical and behavioral effects of corticotropin-releasing factor in the ventral tegmental area of the rat. J Pharmacol Exp Ther 242:757–763

    PubMed  CAS  Google Scholar 

  • Lanteri C, Salomon L, Torrens Y, Glowinski J, Tassin JP (2008) Drugs of abuse specifically sensitize noradrenergic and serotonergic neurons via a non-dopaminergic mechanism. Neuropsychopharmacology 33:1724–1734

    Article  PubMed  CAS  Google Scholar 

  • Leng A, Feldon J, Ferger B (2004) Long-term social isolation and medial prefrontal cortex: dopaminergic and cholinergic neurotransmission. Pharmacol Biochem Behav 77:371–379

    Article  PubMed  CAS  Google Scholar 

  • Lucas LR, Celen Z, Tamashiro KL, Blanchard RJ, Blanchard DC, Markham C, Sakai RR, McEwen BS (2004) Repeated exposure to social stress has long-term effects on indirect markers of dopaminergic activity in brain regions associated with motivated behavior. Neuroscience 124:449–457

    Article  PubMed  CAS  Google Scholar 

  • Marinelli M, Rudick CN, Hu XT, White FJ (2006) Excitability of dopamine neurons: modulation and physiological consequences. CNS Neurol Disord Drug Targets 5:79–97

    Article  PubMed  CAS  Google Scholar 

  • Meerlo P, Overkamp GJ, Benning MA, Koolhaas JM, Van den Hoofdakker RH (1996) Long-term changes in open field behaviour following a single social defeat in rats can be reversed by sleep deprivation. Physiol Behav 60:115–119

    Article  PubMed  CAS  Google Scholar 

  • Miczek KA, Yap JJ, Covington HE 3rd (2008) Social stress, therapeutics and drug abuse: preclinical models of escalated and depressed intake. Pharmacol Ther 120:102–28

    Google Scholar 

  • Morgan D, Grant KA, Gage HD, Mach RH, Kaplan JR, Prioleau O, Nader SH, Buchheimer N, Ehrenkaufer RL, Nader MA (2002) Social dominance in monkeys: dopamine D2 receptors and cocaine self-administration. Nat Neurosci 5:169–174

    Article  PubMed  CAS  Google Scholar 

  • Nielsen EB (1981) Rapid decline of stereotyped behavior in rats during constant one week administration of amphetamine via implanted ALZET osmotic minipumps. Pharmacol Biochem Behav 15:161–165

    Article  PubMed  CAS  Google Scholar 

  • Nikulina EM, Covington HE 3rd, Ganschow L, Hammer RP Jr, Miczek KA (2004) Long-term behavioral and neuronal cross-sensitization to amphetamine induced by repeated brief social defeat stress: Fos in the ventral tegmental area and amygdala. Neuroscience 123:857–865

    Article  PubMed  CAS  Google Scholar 

  • Nordquist RE, Vanderschuren LJ, Jonker AJ, Bergsma M, de Vries TJ, Pennartz CM, Voorn P (2008) Expression of amphetamine sensitization is associated with recruitment of a reactive neuronal population in the nucleus accumbens core. Psychopharmacology (Berl) 198:113–126

    Article  CAS  Google Scholar 

  • Peterson JT, Pohorecky LA (1989) Effect of chronic ethanol administration on intermale aggression in rats. Aggress Behav 15:201–216

    Article  CAS  Google Scholar 

  • Pohorecky LA (1990) The interaction of alcohol and stress: research with experimental animals—an update. Alcohol Alcohol 25:263–276

    PubMed  CAS  Google Scholar 

  • Pohorecky LA (1991) Stress and alcohol interaction: an update of human research. Acohol Clin Exp Res 15:438–459

    Article  CAS  Google Scholar 

  • Pohorecky LA (2006) Housing and rank status of male Long–Evans rats modify ethanol’s effect on open-field behaviors. Psychopharmacology (Berl) 185:289–297

    Article  CAS  Google Scholar 

  • Pohorecky LA (2008) Psychosocial stress and chronic ethanol ingestion in male rats: effects on elevated plus maze behavior and ultrasonic vocalizations. Physiol Behav 9(94):432–447

    Article  Google Scholar 

  • Pohorecky LA, Skiandos A, Zhang X, Rice KC, Benjamin D (1999) Effect of chronic social stress on delta-opioid receptor function in the rat. J Pharmacol Exp Ther 290:196–206

    PubMed  CAS  Google Scholar 

  • Pohorecky LA, Baumann MH, Benjamin D (2004a) Effects of chronic social stress on neuroendocrine responsiveness to challenge with ethanol, dexamethasone and corticotropin-releasing hormone. Neuroendocrinology 80:332–342

    Article  PubMed  CAS  Google Scholar 

  • Pohorecky LA, Blakley GG, Kubovcakova L, Krizanova O, Patterson-Buckendahl P, Kvetnansky R (2004b) Social hierarchy affects gene expression for catecholamine biosynthetic enzymes in rat adrenal glands. Neuroendocrinology 80:42–51

    Article  PubMed  CAS  Google Scholar 

  • Ramos A, Correia EC, Izídio GS, Brüske GR (2003) Genetic selection of two new rat lines displaying different levels of anxiety-related behaviors. Behav Genet 33:657–668

    Article  PubMed  Google Scholar 

  • Ranje C, Ungerstedt U (1977) High correlations between number of dopamine cells, dopamine levels and motor performance. Brain Res 134:83–93

    Article  PubMed  CAS  Google Scholar 

  • Razzoli M, Andreoli M, Michielin F, Quarta D, Sokal DM (2011) Increased phasic activity of VTA dopamine neurons in mice 3 weeks after repeated social defeat. Behav Brain Res 218:253–257

    Article  PubMed  CAS  Google Scholar 

  • Ruis MA, te Brake JH, Buwalda B, De Boer SF, Meerlo P, Korte SM, Blokhuis HJ, Koolhaas JM (1999) Housing familiar male wildtype rats together reduces the long-term adverse behavioural and physiological effects of social defeat. Psychoneuroendocrinology 24:285–300

    Article  PubMed  CAS  Google Scholar 

  • Schmidt MV, Scharf SH, Sterlemann V, Ganea K, Liebl C, Holsboer F, Müller MB (2010) High susceptibility to chronic social stress is associated with a depression-like phenotype. Psychoneuroendocrinology 35:635–643

    Article  PubMed  CAS  Google Scholar 

  • Sciolino NR, Bortolato M, Eisenstein SA, Fu J, Oveisi F, Hohmann AG, Piomelli D (2010) Social isolation and chronic handling alter endocannabinoid signaling and behavioral reactivity to context in adult rats. Neuroscience 168:371–386

    Article  PubMed  CAS  Google Scholar 

  • Segal DS (1976) Differential effects of para-chlorophenylalanine on amphetamine-induced locomotion and stereotypy. Brain Res 116:267–276

    Article  PubMed  CAS  Google Scholar 

  • Smith EO, Byrd LD (1984) Contrasting effects of d-amphetamine on affiliation and aggression in monkeys. Pharmacol Biochem Behav 20:255–260

    Article  PubMed  CAS  Google Scholar 

  • Smith JK, Neill JC, Costall B (1997) Post-weaning housing conditions influence the behavioural effects of cocaine and d-amphetamine. Psychopharmacology (Berl) 131:23–33

    Article  CAS  Google Scholar 

  • Spruijt BM, van Hooff JA, Gispen WH (1992) Ethology and neurobiology of grooming behavior. Physiol Rev 72:825–852

    PubMed  CAS  Google Scholar 

  • Thiel CM, Huston JP, Schwarting RK (1998) Cholinergic activation in frontal cortex and nucleus accumbens related to basic behavioral manipulations: handling, and the role of post-handling experience. Brain Res 812:121–132

    Article  PubMed  CAS  Google Scholar 

  • Tidey JW, Miczek KA (1996) Social defeat stress selectively alters mesocorticolimbic dopamine release: an in vivo microdialysis study. Brain Res 721:140–149

    Article  PubMed  CAS  Google Scholar 

  • Uhart M, Wand GS (2009) Stress, alcohol and drug interaction: an update of human research. Addict Biol 14:43–64

    Article  PubMed  CAS  Google Scholar 

  • Van Erp AM, Kruk MR, Meelis W, Willekens-Bramer DC (1994) Effect of environmental stressors on time course, variability and form of self-grooming in the rat: handling, social contact, defeat, novelty, restraint. Behav Brain Res 65:47–55

    Article  PubMed  Google Scholar 

  • Ventura R, Alcaro A, Cabib S, Conversi D, Mandolesi L, Puglisi-Allegra S (2004) Dopamine in the medial prefrontal cortex controls genotype-dependent effects of amphetamine on mesoaccumbens dopamine release and locomotion. Neuropsychopharmacology 29:72–80

    Article  PubMed  CAS  Google Scholar 

  • Wanat MJ, Hopf FW, Stuber GD, Phillips PE, Bonci A (2008) Corticotropin-releasing factor increases mouse ventral tegmental area dopamine neuron firing through a protein kinase C-dependent enhancement of Ih. J Physiol 15(586):2157–2170

    Article  Google Scholar 

  • Wand GS, Oswald LM, McCaul ME, Wong DF, Johnson E, Zhou Y, Kuwabara H, Kumar A (2007) Association of amphetamine-induced striatal dopamine release and cortisol responses to psychological stress. Neuropsychopharmacology 32:2310–2320

    Article  PubMed  CAS  Google Scholar 

  • West CH, Michael RP (1987) Handling facilitates the acquisition of lever-pressing for brain self-stimulation in the posterior hypothalamus of rats. Physiol Behav 39:77–81

    Article  PubMed  CAS  Google Scholar 

  • Wood SK, Walker HE, Valentino RJ, Bhatnagar S (2010) Individual differences in reactivity to social stress predict susceptibility and resilience to a depressive phenotype: role of corticotropin-releasing factor. Endocrinology 151:1795–1805

    Article  PubMed  CAS  Google Scholar 

  • Zelena D, Haller J, Halász J, Makara GB (1999) Social stress of variable intensity: physiological and behavioral consequences. Brain Res Bull 48:297–302

    Google Scholar 

Download references

Acknowledgment

This research was supported in part by funds from the National Institute of Alcoholism and Alcohol Abuse, Grant 1RO1AA10124 and the Center of Alcohol Studies.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Larissa A. Pohorecky.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pohorecky, L.A., Sweeny, A. & Buckendahl, P. Differential sensitivity to amphetamine’s effect on open field behavior of psychosocially stressed male rats. Psychopharmacology 218, 281–292 (2011). https://doi.org/10.1007/s00213-011-2339-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-011-2339-8

Keywords

Navigation