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Effects of Social Isolation on Perineuronal Nets in the Amygdala Following a Reward Omission Task in Female Rats

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Abstract

Negative urgency is a facet of impulsivity associated with negative affect and risky behavior that may involve the amygdala. The current study determined if social isolation during development alters negative urgency and c-Fos activity in the basolateral amygdala (BLA). Female Sprague-Dawley rats were raised in an isolated condition (IC), a standard social condition (SC), or an enriched condition (EC) and then were tested for locomotor activity, novelty place preference, and negative urgency using a reward omission task. Following performance on the reward omission task, the brains were analyzed for c-Fos expression in Ca2+/calmodulin kinase II (CaMKII) and calbindin (CB) neurons, as well as in parvalbumin (PV) neurons associated with perineuronal nets (PNNs) in BLA. IC rats exhibited enhanced locomotion compared with both SC and EC rats, as well as enhanced novelty place preference compared with EC rats; only IC rats showed increased responding following omission of an expected reward (negative urgency). Following completion of the reward omission task, IC rats also displayed increased percent of c-Fos neurons in BLA associated with CaMKII, CB, and PV neurons compared with SC and EC rats. In IC rats, c-Fos activation in BLA occurred following the omission of an expected reward. Finally, IC rats displayed reduced PNN intensity associated with PV neurons compared with EC rats, but the percent of these neurons co-expressing c-Fos was greater in IC rats; SC rats were intermediate between IC and EC rats. Negative urgency was observed in IC rats, but not SC or EC rats. While multiple mechanisms are likely involved, this behavioral effect was associated with an isolation-induced increase in activity of excitatory neurons in BLA, as well as decreased PNN intensity surrounding GABAergic neurons in the same region.

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References

  1. Jaffee SR, Hanscombe KB, Haworth CM, Davis OS, Plomin R (2012) Chaotic homes and children’s disruptive behavior: a longitudinal cross-lagged twin study. Psychol Sci 23:643–650

    PubMed  PubMed Central  Google Scholar 

  2. Gipson CD, Beckmann JS, El-Maraghi S, Marusich JA, Bardo MT (2011) Effect of environmental enrichment on escalation of cocaine self-administration in rats. Psychopharmacology 214:557–566

    CAS  PubMed  Google Scholar 

  3. Bardo MT, Klebaur JE, Valone JM, Deaton C (2001) Environmental enrichment decreases intravenous self-administration of amphetamine in female and male rats. Psychopharmacology 155:278–284

    CAS  PubMed  Google Scholar 

  4. Green TA, Gehrke BJ, Bardo MT (2002) Environmental enrichment decreases intravenous amphetamine self-administration in rats: dose-response functions for fixed- and progressive-ratio schedules. Psychopharmacology 162:373–378

    CAS  PubMed  Google Scholar 

  5. Bardo MT, Dwoskin LP (2004) Biological connection between novelty- and drug-seeking motivational systems. Nebraska Symp Motiv Nebraska Symp Motiv 50:127–158

    Google Scholar 

  6. Cain ME, Green TA, Bardo MT (2006) Environmental enrichment decreases responding for visual novelty. Behav Process 73:360–366

    Google Scholar 

  7. Slaker M, Barnes J, Sorg BA, Grimm JW (2016) Impact of environmental enrichment on perineuronal nets in the prefrontal cortex following early and late abstinence from sucrose self-administration in rats. PLoS One 11:e0168256

    PubMed  PubMed Central  Google Scholar 

  8. van Praag H, Kempermann G, Gage FH (2000) Neural consequences of environmental enrichment. Nat Rev Neurosci 1:191–198

    PubMed  Google Scholar 

  9. Hofford RS, Chow JJ, Beckmann JS, Bardo MT (2017) Effects of environmental enrichment on self-administration of the short-acting opioid remifentanil in male rats. Psychopharmacology 234:3499–3506

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Mumtaz F, Khan MI, Zubair M, Dehpour AR (2018) Neurobiology and consequences of social isolation stress in animal model-a comprehensive review. Biomed Pharmacother 105:1205–1222

    CAS  PubMed  Google Scholar 

  11. Chauvet C, Lardeux V, Jaber M, Solinas M (2011) Brain regions associated with the reversal of cocaine conditioned place preference by environmental enrichment. Neuroscience 184:88–96

    CAS  PubMed  Google Scholar 

  12. Grimm JW, Barnes JL, Koerber J, Glueck E, Ginder D, Hyde J, Eaton L (2016) Effects of acute or chronic environmental enrichment on regional Fos protein expression following sucrose cue-reactivity testing in rats. Brain Struct Funct 221:2817–2830

    CAS  PubMed  Google Scholar 

  13. Whiteside SP, Lynam DR (2003) Understanding the role of impulsivity and externalizing psychopathology in alcohol abuse: application of the UPPS impulsive behavior scale. Exp Clin Psychopharmacol 11:210–217

    PubMed  Google Scholar 

  14. Wills TA, Vaccaro D, McNamara G (1994) Novelty seeking, risk taking, and related constructs as predictors of adolescent substance use: an application of Cloninger’s theory. J Subst Abus 6:1–20

    CAS  Google Scholar 

  15. Bardo MT, Donohew RL, Harrington NG (1996) Psychobiology of novelty seeking and drug seeking behavior. Behav Brain Res 77:23–43

    CAS  PubMed  Google Scholar 

  16. Tran J, Teese R, Gill PR (2018) UPPS-P facets of impulsivity and alcohol use patterns in college and noncollege emerging adults. Am J Drug Alcohol Abuse 44:695–704

    PubMed  Google Scholar 

  17. Cyders MA, Smith GT (2008) Emotion-based dispositions to rash action: positive and negative urgency. Psychol Bull 134:807–828

    PubMed  PubMed Central  Google Scholar 

  18. Beckmann JS, Marusich JA, Gipson CD, Bardo MT (2011) Novelty seeking, incentive salience and acquisition of cocaine self-administration in the rat. Behav Brain Res 216:159–165

    CAS  PubMed  Google Scholar 

  19. Dellu F, Piazza PV, Mayo W, Le Moal M, Simon H (1996) Novelty-seeking in rats--biobehavioral characteristics and possible relationship with the sensation-seeking trait in man. Neuropsychobiology 34:136–145

    CAS  PubMed  Google Scholar 

  20. Gipson CD, Beckmann JS, Adams ZW, Marusich JA, Nesland TO, Yates JR, Kelly TH, Bardo MT (2012) A translational behavioral model of mood-based impulsivity: implications for substance abuse. Drug Alcohol Depend 122:93–99

    PubMed  Google Scholar 

  21. Yates JR, Darna M, Gipson CD, Dwoskin LP, Bardo MT (2015) Dissociable roles of dopamine and serotonin transporter function in a rat model of negative urgency. Behav Brain Res 291:201–208

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Um M, Whitt ZT, Revilla R, Hunton T, Cyders MA (2019) Shared neural correlates underlying addictive disorders and negative urgency. Brain Sci 9(2):36. https://doi.org/10.3390/brainsci9020036

  23. Cyders MA, Dzemidzic M, Eiler WJ, Coskunpinar A, Karyadi KA, Kareken DA (2015) Negative urgency mediates the relationship between amygdala and orbitofrontal cortex activation to negative emotional stimuli and general risk-taking. Cereb Cortex (New York, NY : 1991) 25:4094–4102

    Google Scholar 

  24. Pizzorusso T, Medini P, Berardi N, Chierzi S, Fawcett JW, Maffei L (2002) Reactivation of ocular dominance plasticity in the adult visual cortex. Science (New York, NY) 298:1248–1251

    CAS  Google Scholar 

  25. Slaker M, Churchill L, Todd RP, Blacktop JM, Zuloaga DG, Raber J, Darling RA, Brown TE et al (2015) Removal of perineuronal nets in the medial prefrontal cortex impairs the acquisition and reconsolidation of a cocaine-induced conditioned place preference memory. J Neurosci 35:4190–4202

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Vazquez-Sanroman DB, Monje RD, Bardo MT (2017) Nicotine self-administration remodels perineuronal nets in ventral tegmental area and orbitofrontal cortex in adult male rats. Addict Biol 22:1743–1755

    CAS  PubMed  Google Scholar 

  27. Vazquez-Sanroman D, Carbo-Gas M, Leto K, Cerezo-Garcia M, Gil-Miravet I, Sanchis-Segura C, Carulli D, Rossi F et al (2015) Cocaine-induced plasticity in the cerebellum of sensitised mice. Psychopharmacology 232:4455–4467

    CAS  PubMed  Google Scholar 

  28. Gogolla N, Caroni P, Luthi A, Herry C (2009) Perineuronal nets protect fear memories from erasure. Science (New York, NY) 325:1258–1261

    CAS  Google Scholar 

  29. Burgos-Robles A, Kimchi EY, Izadmehr EM, Porzenheim MJ, Ramos-Guasp WA, Nieh EH, Felix-Ortiz AC, Namburi P et al (2017) Amygdala inputs to prefrontal cortex guide behavior amid conflicting cues of reward and punishment. Nat Neurosci 20:824–835

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Wassum KM, Izquierdo A (2015) The basolateral amygdala in reward learning and addiction. Neurosci Biobehav Rev 57:271–283

    PubMed  PubMed Central  Google Scholar 

  31. Lynch WJ (2018) Modeling the development of drug addiction in male and female animals. Pharmacol Biochem Behav 164:50–61

    CAS  PubMed  Google Scholar 

  32. Anker JJ, Carroll ME (2011) Females are more vulnerable to drug abuse than males: evidence from preclinical studies and the role of ovarian hormones. Curr Top Behav Neurosci 8:73–96

    CAS  PubMed  Google Scholar 

  33. Marusich JA, Darna M, Charnigo RJ, Dwoskin LP, Bardo MT (2011) A multivariate assessment of individual differences in sensation seeking and impulsivity as predictors of amphetamine self-administration and prefrontal dopamine function in rats. Exp Clin Psychopharmacol 19:275–284

    PubMed  PubMed Central  Google Scholar 

  34. Paxinos G, Watson C (2016) The rat brain in stereotaxic coordinates. Academic Press/Elsevier, Amsterdam

  35. Reznikov LR, Reagan LP, Fadel JR (2008) Activation of phenotypically distinct neuronal subpopulations in the anterior subdivision of the rat basolateral amygdala following acute and repeated stress. J Comp Neurol 508:458–472

    PubMed  Google Scholar 

  36. Thompson EH, Lensjo KK, Wigestrand MB, Malthe-Sorenssen A, Hafting T, Fyhn M (2018) Removal of perineuronal nets disrupts recall of a remote fear memory. Proc Natl Acad Sci U S A 115:607–612

    CAS  PubMed  Google Scholar 

  37. Grimm JW, Sauter F (2020) Environmental enrichment reduces food seeking and taking in rats: a review. Pharmacol Biochem Behav 190:172874

    CAS  PubMed  Google Scholar 

  38. Elliott BM, Grunberg NE (2005) Effects of social and physical enrichment on open field activity differ in male and female Sprague-Dawley rats. Behav Brain Res 165:187–196

    PubMed  Google Scholar 

  39. Bowling SL, Bardo MT (1994) Locomotor and rewarding effects of amphetamine in enriched, social, and isolate reared rats. Pharmacol Biochem Behav 48:459–464

    CAS  PubMed  Google Scholar 

  40. Smith GT, Cyders MA (2016) Integrating affect and impulsivity: the role of positive and negative urgency in substance use risk. Drug Alcohol Depend 163(Suppl 1):S3–s12

    PubMed  PubMed Central  Google Scholar 

  41. Stairs DJ, Bardo MT (2009) Neurobehavioral effects of environmental enrichment and drug abuse vulnerability. Pharmacol Biochem Behav 92:377–382

    CAS  PubMed  PubMed Central  Google Scholar 

  42. McAllister DE, McAllister WR, Zellner DK (1966) Preference for familiar stimuli in the rat. Psychol Rep 19:868–870

    Google Scholar 

  43. Green TA, Alibhai IN, Roybal CN, Winstanley CA, Theobald DE, Birnbaum SG, Graham AR, Unterberg S et al (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

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Rowniak M, Bogus-Nowakowska K, Robak A (1604) The densities of calbindin and parvalbumin, but not calretinin neurons, are sexually dimorphic in the amygdala of the guinea pig. Brain Res 2015:84–97

    Google Scholar 

  45. Chen Y, Jiang Y, Yue W, Zhou Y, Lu L, Ma L (2008) Chronic, but not acute morphine treatment, up-regulates alpha-Ca2+/calmodulin dependent protein kinase II gene expression in rat brain. Neurochem Res 33:2092–2098

    CAS  PubMed  Google Scholar 

  46. Morikawa S, Ikegaya Y, Narita M, Tamura H (2017) Activation of perineuronal net-expressing excitatory neurons during associative memory encoding and retrieval. Sci Rep 7:46024

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Liu XH, Zhu RT, Hao B, Shi YW, Wang XG, Xue L, Zhao H (2019) Norepinephrine induces PTSD-like memory impairments via regulation of the beta-adrenoceptor-cAMP/PKA and CaMK II/PKC systems in the basolateral amygdala. Front Behav Neurosci 13:43

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Slaker M, Blacktop JM, Sorg BA (2016) Caught in the net: perineuronal nets and addiction. Neural Plast 2016:7538208

    PubMed  PubMed Central  Google Scholar 

  49. Sorg BA, Berretta S, Blacktop JM, Fawcett JW, Kitagawa H, Kwok JC, Miquel M (2016) Casting a wide net: role of perineuronal nets in neural plasticity. J Neurosci 36:11459–11468

    CAS  PubMed  PubMed Central  Google Scholar 

  50. O’Connor AM, Burton TJ, Mansuri H, Hand GR, Leamey CA, Sawatari A (2019) Environmental enrichment from birth impacts parvalbumin expressing cells and wisteria floribunda agglutinin labelled peri-neuronal nets within the developing murine striatum. Front Neuroanat 13:90

    PubMed  PubMed Central  Google Scholar 

  51. Yamada J, Ohgomori T, Jinno S (2015) Perineuronal nets affect parvalbumin expression in GABAergic neurons of the mouse hippocampus. Eur J Neurosci 41:368–378

    CAS  PubMed  Google Scholar 

  52. Calu DJ, Roesch MR, Haney RZ, Holland PC, Schoenbaum G (2010) Neural correlates of variations in event processing during learning in central nucleus of amygdala. Neuron 68:991–1001

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Sharpe MJ, Schoenbaum G (2016) Back to basics: making predictions in the orbitofrontal-amygdala circuit. Neurobiol Learn Mem 131:201–206

    PubMed  PubMed Central  Google Scholar 

  54. Iordanova MD, Deroche ML, Esber GR, Schoenbaum G (2016) Neural correlates of two different types of extinction learning in the amygdala central nucleus. Nat Commun 7:12330

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We thank Emily Denehy and Seth Mayfield for technical support. We thank Drs. Mark Prendergast and James Pauly for allowing us the use of equipment.

Funding

This work was supported by NIH grants P50 DA05312 (MB) and R01 DA12964 (MB) and Start Funds DVS-Oklahoma State University Center for Health and Sciences.

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Authors and Affiliations

  1. Anatomy and Cell Biology Department, Oklahoma State University, Tulsa, OK, 74107, USA

    Dolores B. Vazquez-Sanroman

  2. Booz Allen Hamilton, McLean, VA, USA

    G. Arlington Wilson

  3. Department of Psychology, University of Kentucky, Lexington, KY, 40536, USA

    M. T. Bardo

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  1. Dolores B. Vazquez-Sanroman
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  2. G. Arlington Wilson
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  3. M. T. Bardo
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Correspondence to Dolores B. Vazquez-Sanroman.

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All procedures were approved by the University of Kentucky Institutional Animal Care and Use Committee and conformed to NIH guidelines.

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Supplementary Figure 1

A. Schematic for baseline acquisition in reward omission task. B. Schematic for testing in reward omission task. C. Photos are representative confocal images co-labeled with CaMKII+ and WFA+ illustrating absence of colocalization of glutamatergic neurons and PNNs. (PNG 1561 kb)

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Vazquez-Sanroman, D.B., Arlington Wilson, G. & Bardo, M.T. Effects of Social Isolation on Perineuronal Nets in the Amygdala Following a Reward Omission Task in Female Rats. Mol Neurobiol 58, 348–361 (2021). https://doi.org/10.1007/s12035-020-02125-8

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