Skip to main content

Advertisement

SpringerLink
Log in

Chronic wheel running-induced reduction of extinction and reinstatement of methamphetamine seeking in methamphetamine dependent rats is associated with reduced number of periaqueductal gray dopamine neurons

  • Original Article
  • Published:
Brain Structure and Function Aims and scope Submit manuscript

Abstract

Exercise (physical activity) has been proposed as a treatment for drug addiction. In rodents, voluntary wheel running reduces cocaine and nicotine seeking during extinction, and reinstatement of cocaine seeking triggered by drug-cues. The purpose of this study was to examine the effects of chronic wheel running during withdrawal and protracted abstinence on extinction and reinstatement of methamphetamine seeking in methamphetamine dependent rats, and to determine a potential neurobiological correlate underlying the effects. Rats were given extended access to methamphetamine (0.05 mg/kg, 6 h/day) for 22 sessions. Rats were withdrawn and were given access to running wheels (wheel runners) or no wheels (sedentary) for 3 weeks after which they experienced extinction and reinstatement of methamphetamine seeking. Extended access to methamphetamine self-administration produced escalation in methamphetamine intake. Methamphetamine experience reduced running output, and conversely, access to wheel running during withdrawal reduced responding during extinction and, context- and cue-induced reinstatement of methamphetamine seeking. Immunohistochemical analysis of brain tissue demonstrated that wheel running during withdrawal did not regulate markers of methamphetamine neurotoxicity (neurogenesis, neuronal nitric oxide synthase, vesicular monoamine transporter-2) and cellular activation (c-Fos) in brain regions involved in relapse to drug seeking. However, reduced methamphetamine seeking was associated with running-induced reduction (and normalization) of the number of tyrosine hydroxylase immunoreactive neurons in the periaqueductal gray (PAG). The present study provides evidence that dopamine neurons of the PAG region show adaptive biochemical changes during methamphetamine seeking in methamphetamine dependent rats and wheel running abolishes these effects. Given that the PAG dopamine neurons project onto the structures of the extended amygdala, the present findings also suggest that wheel running may be preventing certain allostatic changes in the brain reward and stress systems contributing to the negative reinforcement and perpetuation of the addiction cycle.

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

Access this article

Log in via an institution

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

Similar content being viewed by others

References

  • Bandler R, Shipley MT (1994) Columnar organization in the midbrain periaqueductal gray: modules for emotional expression? Trends Neurosci 17:379–389

    Article  PubMed  CAS  Google Scholar 

  • Berchtold NC, Chinn G, Chou M, Kesslak JP, Cotman CW (2005) Exercise primes a molecular memory for brain-derived neurotrophic factor protein induction in the rat hippocampus. Neuroscience 133:853–861

    Article  PubMed  CAS  Google Scholar 

  • Bjorklund L, Stromberg I (1997) Dopaminergic innervation of striatal grafts placed into different sites of normal striatum: differences in the tyrosine hydroxylase immunoreactive growth pattern. Exp Brain Res 113:13–23

    Article  PubMed  CAS  Google Scholar 

  • Bock BC, Marcus BH, King TK, Borrelli B, Roberts MR (1999) Exercise effects on withdrawal and mood among women attempting smoking cessation. Addict Behav 24:399–410

    Article  PubMed  CAS  Google Scholar 

  • Boger HA, Middaugh LD, Granholm AC, McGinty JF (2009) Minocycline restores striatal tyrosine hydroxylase in GDNF heterozygous mice but not in methamphetamine-treated mice. Neurobiol Dis 33:459–466

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Carroll KM, Rounsaville BJ, Nich C, Gordon LT, Wirtz PW, Gawin F (1994) One-year follow-up of psychotherapy and pharmacotherapy for cocaine dependence. Delayed emergence of psychotherapy effects. Arch Gen Psychiatry 51:989–997

    Article  PubMed  CAS  Google Scholar 

  • Casu MA, Colombo G, Gessa GL, Pani L (2002) Reduced TH-immunoreactive fibers in the limbic system of Sardinian alcohol-preferring rats. Brain Res 924:242–251

    Article  PubMed  CAS  Google Scholar 

  • Clark PJ, Bhattacharya TK, Miller DS, Rhodes JS (2011) Induction of c-Fos, Zif268, and Arc from acute bouts of voluntary wheel running in new and pre-existing adult mouse hippocampal granule neurons. Neuroscience 184:16–27

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Clark PJ, Bhattacharya TK, Miller DS, Kohman RA, Deyoung EK, Rhodes JS (2012) New neurons generated from running are broadly recruited into neuronal activation associated with three different hippocampus-involved tasks. Hippocampus 22:1860–1867

    Article  PubMed Central  PubMed  Google Scholar 

  • Cryan JF, Hoyer D, Markou A (2003) Withdrawal from chronic amphetamine induces depressive-like behavioral effects in rodents. Biol Psychiatry 54:49–58

    Article  PubMed  CAS  Google Scholar 

  • Eisch AJ, Harburg GC (2006) Opiates, psychostimulants, and adult hippocampal neurogenesis: insights for addiction and stem cell biology. Hippocampus 16:271–286

    Article  PubMed  CAS  Google Scholar 

  • Eisch AJ, Barrot M, Schad CA, Self DW, Nestler EJ (2000) Opiates inhibit neurogenesis in the adult rat hippocampus. Proc Natl Acad Sci USA 97:7579–7584

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Engelmann AJ, Aparicio MB, Kim A, Sobieraj JC, Yuan CJ, Grant Y, Mandyam CD (2013) Chronic wheel running reduces maladaptive patterns of methamphetamine intake: regulation by attenuation of methamphetamine-induced neuronal nitric oxide synthase. Brain Struct Funct 219:657–672

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Epstein DH, Preston KL, Stewart J, Shaham Y (2006) Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure. Psychopharmacology 189:1–16

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Eyerman DJ, Yamamoto BK (2007) A rapid oxidation and persistent decrease in the vesicular monoamine transporter 2 after methamphetamine. J Neurochem 103:1219–1227

    Article  PubMed  CAS  Google Scholar 

  • Farmer J, Zhao X, van Praag H, Wodtke K, Gage FH, Christie BR (2004) Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo. Neuroscience 124:71–79

    Article  PubMed  CAS  Google Scholar 

  • Fillipas S, Oldmeadow LB, Bailey MJ, Cherry CL (2006) A six-month, supervised, aerobic and resistance exercise program improves self-efficacy in people with human immunodeficiency virus: a randomised controlled trial. Aust J Physiother 52:185–190

    Article  PubMed  Google Scholar 

  • Freedman LJ, Cassell MD (1994) Distribution of dopaminergic fibers in the central division of the extended amygdala of the rat. Brain Res 633:243–252

    Article  PubMed  CAS  Google Scholar 

  • Fuchs RA, Evans KA, Ledford CC, Parker MP, Case JM, Mehta RH, See RE (2005) The role of the dorsomedial prefrontal cortex, basolateral amygdala, and dorsal hippocampus in contextual reinstatement of cocaine seeking in rats. Neuropsychopharmacology 30:296–309

    Article  PubMed  CAS  Google Scholar 

  • Fuchs RA, Eaddy JL, Su ZI, Bell GH (2007) Interactions of the basolateral amygdala with the dorsal hippocampus and dorsomedial prefrontal cortex regulate drug context-induced reinstatement of cocaine-seeking in rats. Eur J Neurosci 26:487–498

    Article  PubMed  Google Scholar 

  • Gonzales R, Mooney L, Rawson RA (2010) The methamphetamine problem in the United States. Annu Rev Public Health 31:385–398

    Article  PubMed Central  PubMed  Google Scholar 

  • Grove EA (1988) Neural associations of the substantia innominata in the rat: afferent connections. J Comp Neurol 277:315–346

    Article  PubMed  CAS  Google Scholar 

  • Harris GC, Aston-Jones G (1994) Involvement of D2 dopamine receptors in the nucleus accumbens in the opiate withdrawal syndrome. Nature 371:155–157

    Article  PubMed  CAS  Google Scholar 

  • Hasue RH, Shammah-Lagnado SJ (2002) Origin of the dopaminergic innervation of the central extended amygdala and accumbens shell: a combined retrograde tracing and immunohistochemical study in the rat. J Comp Neurol 454:15–33

    Article  PubMed  CAS  Google Scholar 

  • Hiranita T, Nawata Y, Sakimura K, Anggadiredja K, Yamamoto T (2006) Suppression of methamphetamine-seeking behavior by nicotinic agonists. Proc Natl Acad Sci USA 103:8523–8527

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Hofford RS, Darna M, Wilmouth CE, Dwoskin LP, Bardo MT (2014) Environmental enrichment reduces methamphetamine cue-induced reinstatement but does not alter methamphetamine reward or VMAT2 function. Behav Brain Res 270:151–158

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Hyman SE, Kosofsky BE, Nguyen TV, Cohen BM, Comb MJ (1993) Everything activates c-fos–how can it matter? NIDA Res Monogr 125:25–38

    PubMed  CAS  Google Scholar 

  • Johnson RA, Mitchell GS (2003) Exercise-induced changes in hippocampal brain-derived neurotrophic factor and neurotrophin-3: effects of rat strain. Brain Res 983:108–114

    Article  PubMed  CAS  Google Scholar 

  • Kalivas PW, McFarland K (2003) Brain circuitry and the reinstatement of cocaine-seeking behavior. Psychopharmacology 168:44–56

    Article  PubMed  CAS  Google Scholar 

  • Kanarek RB, Marks-Kaufman R, D’Anci KE, Przypek J (1995) Exercise attenuates oral intake of amphetamine in rats. Pharmacol Biochem Behav 51:725–729

    Article  PubMed  CAS  Google Scholar 

  • Keller CM, Salvatore MF, Pruett BS, Guerin GF, Goeders NE (2011) Biphasic dopamine regulation in mesoaccumbens pathway in response to non-contingent binge and escalating methamphetamine regimens in the Wistar rat. Psychopharmacology 215:513–526

    Article  PubMed  CAS  Google Scholar 

  • Kitamura O, Wee S, Specio SE, Koob GF, Pulvirenti L (2006) Escalation of methamphetamine self-administration in rats: a dose-effect function. Psychopharmacology 186:48–53

    Article  PubMed  CAS  Google Scholar 

  • Koob GF (2013) Addiction is a Reward Deficit and Stress Surfeit Disorder. Front Psychiatry 4:72

    Article  PubMed Central  PubMed  Google Scholar 

  • Korhonen T, Kujala UM, Rose RJ, Kaprio J (2009) Physical activity in adolescence as a predictor of alcohol and illicit drug use in early adulthood: a longitudinal population-based twin study. Twin Res Hum Genet 12:261–268

    Article  PubMed Central  PubMed  Google Scholar 

  • Krasnova IN, Justinova Z, Ladenheim B, Jayanthi S, McCoy MT, Barnes C, Warner JE, Goldberg SR, Cadet JL (2010) Methamphetamine self-administration is associated with persistent biochemical alterations in striatal and cortical dopaminergic terminals in the rat. PLoS One 5:e8790

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kujala UM, Kaprio J, Rose RJ (2007) Physical activity in adolescence and smoking in young adulthood: a prospective twin cohort study. Addiction 102:1151–1157

    Article  PubMed Central  PubMed  Google Scholar 

  • Larsen KE, Fon EA, Hastings TG, Edwards RH, Sulzer D (2002) Methamphetamine-induced degeneration of dopaminergic neurons involves autophagy and upregulation of dopamine synthesis. J Neurosci 22:8951–8960

    PubMed  CAS  Google Scholar 

  • Li YQ, Takada M, Shinonaga Y, Mizuno N (1993) The sites of origin of dopaminergic afferent fibers to the lateral habenular nucleus in the rat. J Comp Neurol 333:118–133

    Article  PubMed  CAS  Google Scholar 

  • Lin TW, Chen SJ, Huang TY, Chang CY, Chuang JI, Wu FS, Kuo YM, Jen CJ (2012) Different types of exercise induce differential effects on neuronal adaptations and memory performance. Neurobiol Learn Mem 97:140–147

    Article  PubMed  Google Scholar 

  • Lynch WJ, Piehl KB, Acosta G, Peterson AB, Hemby SE (2010) Aerobic exercise attenuates reinstatement of cocaine-seeking behavior and associated neuroadaptations in the prefrontal cortex. Biol Psychiatry 68:774–777

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Lynch WJ, Peterson AB, Sanchez V, Abel J, Smith MA (2013) Exercise as a novel treatment for drug addiction: a neurobiological and stage-dependent hypothesis. Neurosci Biobehav Rev 37:1622–1644

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Mandyam CD, Koob GF (2012) The addicted brain craves new neurons: putative role for adult-born progenitors in promoting recovery. Trends Neurosci 35:250–260

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Mandyam CD, Norris RD, Eisch AJ (2004) Chronic morphine induces premature mitosis of proliferating cells in the adult mouse subgranular zone. J Neurosci Res 76:783–794

    Article  PubMed  CAS  Google Scholar 

  • Mandyam CD, Wee S, Eisch AJ, Richardson HN, Koob GF (2007) Methamphetamine self-administration and voluntary exercise have opposing effects on medial prefrontal cortex gliogenesis. J Neurosci 27:11442–11450

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Mandyam CD, Wee S, Crawford EF, Eisch AJ, Richardson HN, Koob GF (2008) Varied access to intravenous methamphetamine self-administration differentially alters adult hippocampal neurogenesis. Biol Psychiatry 64:958–965

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Manger TA, Motta RW (2005) The impact of an exercise program on posttraumatic stress disorder, anxiety, and depression. Int J Emerg Ment Health 7:49–57

    PubMed  Google Scholar 

  • Mantsch JR, Weyer A, Vranjkovic O, Beyer CE, Baker DA, Caretta H (2010) Involvement of noradrenergic neurotransmission in the stress- but not cocaine-induced reinstatement of extinguished cocaine-induced conditioned place preference in mice: role for beta-2 adrenergic receptors. Neuropsychopharmacology 35:2165–2178

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • McFadden LM, Stout KA, Vieira-Brock PL, Allen SC, Nielsen SM, Wilkins DG, Hanson GR, Fleckenstein AE (2012a) Methamphetamine self-administration acutely decreases monoaminergic transporter function. Synapse 66:240–245

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • McFadden LM, Hadlock GC, Allen SC, Vieira-Brock PL, Stout KA, Ellis JD, Hoonakker AJ, Andrenyak DM, Nielsen SM, Wilkins DG, Hanson GR, Fleckenstein AE (2012b) Methamphetamine self-administration causes persistent striatal dopaminergic alterations and mitigates the deficits caused by a subsequent methamphetamine exposure. J Pharmacol Exp Ther 340:295–303

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Messanvi F, Eggens-Meijer E, Roozendaal B, van der Want JJ (2013) A discrete dopaminergic projection from the incertohypothalamic A13 cell group to the dorsolateral periaqueductal gray in rat. Front Neuroanat 7:41

    PubMed Central  PubMed  Google Scholar 

  • Miller ML, Vaillancourt BD, Wright MJ Jr, Aarde SM, Vandewater SA, Creehan KM, Taffe MA (2011) Reciprocal inhibitory effects of intravenous d-methamphetamine self-administration and wheel activity in rats. Drug Alcohol Depend 121:90–96

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Mohawk JA, Menaker M (2009) A new (and different) circadian pacemaker. Cell Cycle 8:2861–2862

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Nawata Y, Kitaichi K, Yamamoto T (2012) Increases of CRF in the amygdala are responsible for reinstatement of methamphetamine-seeking behavior induced by footshock. Pharmacol Biochem Behav 101:297–302

    Article  PubMed  CAS  Google Scholar 

  • NIDA (2006) Research reports: methamphetamine abuse and addiction. Sci Drug Abus Addict

  • NIDA (2010) Drug Facts: methamphetamine. Sci Drug Abus Addict

  • NIDA (2011) Topics in brief: methamphetamine addiction: progress, but need to remain vigilant. Sci Drug Abus Addict

  • Noori HR, Fornal CA (2011) The appropriateness of unbiased optical fractionators to assess cell proliferation in the adult hippocampus. Front Neurosci 5:140

    Article  PubMed Central  PubMed  Google Scholar 

  • Orio L, Wee S, Newman AH, Pulvirenti L, Koob GF (2010) The dopamine D3 receptor partial agonist CJB090 and antagonist PG01037 decrease progressive ratio responding for methamphetamine in rats with extended-access. Addict Biol 15:312–323

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Ottersen OP (1981) Afferent connections to the amygdaloid complex of the rat with some observations in the cat. III. Afferents from the lower brain stem. J Comp Neurol 202:335–356

    Article  PubMed  CAS  Google Scholar 

  • Paxinos G, Watson C (1997) The rat brain in stereotaxic coordinates, 3, edition edn. Academic Press, San Diego

    Google Scholar 

  • Pendergast JS, Yamazaki S (2014) Effects of light, food, and methamphetamine on the circadian activity rhythm in mice. Physiol Behav 128:92–98

    Article  PubMed  CAS  Google Scholar 

  • Peterson AB, Abel JM, Lynch WJ (2013) Dose-dependent effects of wheel running on cocaine-seeking and prefrontal cortex Bdnf exon IV expression in rats. Psychopharmacol (Berl) 231:1305–1314

    Article  CAS  Google Scholar 

  • Recinto P, Samant AR, Chavez G, Kim A, Yuan CJ, Soleiman M, Grant Y, Edwards S, Wee S, Koob GF, George O, Mandyam CD (2012) Levels of neural progenitors in the hippocampus predict memory impairment and relapse to drug seeking as a function of excessive methamphetamine self-administration. Neuropsychopharmacology 37:1275–1287

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Ricaurte GA, Guillery RW, Seiden LS, Schuster CR, Moore RY (1982) Dopamine nerve terminal degeneration produced by high doses of methylamphetamine in the rat brain. Brain Res 235:93–103

    Article  PubMed  CAS  Google Scholar 

  • Rogers JL, De Santis S, See RE (2008) Extended methamphetamine self-administration enhances reinstatement of drug seeking and impairs novel object recognition in rats. Psychopharmacology 199:615–624

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • SAMHSA (2008) Results from the 2007 National Survey on Drug Use and Health: Detailed Tables. Substance Abuse and Mental Health Services Administration, Office of Applied Studies

  • Sanchez V, Moore CF, Brunzell DH, Lynch WJ (2013) Effect of wheel-running during abstinence on subsequent nicotine-seeking in rats. Psychopharmacology 227:403–411

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Schwendt M, Rocha A, See RE, Pacchioni AM, McGinty JF, Kalivas PW (2009) Extended methamphetamine self-administration in rats results in a selective reduction of dopamine transporter levels in the prefrontal cortex and dorsal striatum not accompanied by marked monoaminergic depletion. J Pharmacol Exp Ther 331:555–562

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • See RE, Kruzich PJ, Grimm JW (2001) Dopamine, but not glutamate, receptor blockade in the basolateral amygdala attenuates conditioned reward in a rat model of relapse to cocaine-seeking behavior. Psychopharmacology 154:301–310

    Article  PubMed  CAS  Google Scholar 

  • Segal DS, Kuczenski R (2006) Human methamphetamine pharmacokinetics simulated in the rat: single daily intravenous administration reveals elements of sensitization and tolerance. Neuropsychopharmacology 31:941–955

    Article  PubMed  CAS  Google Scholar 

  • Serwatkiewicz C, Limebeer C, Eikelboom R (2000) Sensitization of amphetamine-induced wheel running suppression in rats: dose and context factors. Psychopharmacology 151:219–225

    Article  PubMed  CAS  Google Scholar 

  • Shaham Y, Shalev U, Lu L, De Wit H, Stewart J (2003) The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology 168:3–20

    Article  PubMed  CAS  Google Scholar 

  • Shepard JD, Chuang DT, Shaham Y, Morales M (2006) Effect of methamphetamine self-administration on tyrosine hydroxylase and dopamine transporter levels in mesolimbic and nigrostriatal dopamine pathways of the rat. Psychopharmacology 185:505–513

    Article  PubMed  CAS  Google Scholar 

  • Smith RJ, Aston-Jones G (2011) alpha(2) Adrenergic and imidazoline receptor agonists prevent cue-induced cocaine seeking. Biol Psychiatry 70:712–719

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Smith MA, Lynch WJ (2011) Exercise as a potential treatment for drug abuse: evidence from preclinical studies. Front Psychiatry 2:82

    Article  PubMed Central  PubMed  Google Scholar 

  • Stefanski R, Lee SH, Yasar S, Cadet JL, Goldberg SR (2002) Lack of persistent changes in the dopaminergic system of rats withdrawn from methamphetamine self-administration. Eur J Pharmacol 439:59–68

    Article  PubMed  CAS  Google Scholar 

  • Stinus L, Le Moal M, Koob GF (1990) Nucleus accumbens and amygdala are possible substrates for the aversive stimulus effects of opiate withdrawal. Neuroscience 37:767–773

    Article  PubMed  CAS  Google Scholar 

  • Tataroglu O, Davidson AJ, Benvenuto LJ, Menaker M (2006) The methamphetamine-sensitive circadian oscillator (MASCO) in mice. J Biol Rhythms 21:185–194

    Article  PubMed  CAS  Google Scholar 

  • Terry-McElrath YM, O’Malley PM (2011) Substance use and exercise participation among young adults: parallel trajectories in a national cohort-sequential study. Addiction 106:1855–1865 (discussion 1866–1857)

    Article  PubMed Central  PubMed  Google Scholar 

  • Terry-McElrath YM, O’Malley PM, Johnston LD (2011) Exercise and substance use among American youth, 1991–2009. Am J Prev Med 40:530–540

    Article  PubMed Central  PubMed  Google Scholar 

  • Thanos PK, Stamos J, Robison LS, Heyman G, Tucci A, Wang GJ, Robinson JK, Anderson BJ, Volkow ND (2013) Daily treadmill exercise attenuates cocaine cue-induced reinstatement and cocaine induced locomotor response but increases cocaine-primed reinstatement. Behav Brain Res 239:8–14

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • USPSTF (2008) United States Preventive Services Task Force (USPSTF) Screening for illicit drug use

  • Valdez GR, Zorrilla EP, Rivier J, Vale WW, Koob GF (2003) Locomotor suppressive and anxiolytic-like effects of urocortin 3, a highly selective type 2 corticotropin-releasing factor agonist. Brain Res 980:206–212

    Article  PubMed  CAS  Google Scholar 

  • van Praag H, Kempermann G, Gage FH (1999a) Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2:266–270

    Article  PubMed  Google Scholar 

  • van Praag H, Christie BR, Sejnowski TJ, Gage FH (1999b) Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci USA 96:13427–13431

    Article  PubMed Central  PubMed  Google Scholar 

  • Wang J, Angulo JA (2011) Synergism between methamphetamine and the neuropeptide substance P on the production of nitric oxide in the striatum of mice. Brain Res 1369:131–139

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Weinstock J, Barry D, Petry NM (2008) Exercise-related activities are associated with positive outcome in contingency management treatment for substance use disorders. Addict Behav 33:1072–1075

    Article  PubMed Central  PubMed  Google Scholar 

  • WHO (1980) Guide to drug abuse epidemiology.

  • Yuan CJ, Quiocho JM, Kim A, Wee S, Mandyam CD (2011) Extended access methamphetamine decreases immature neurons in the hippocampus which results from loss and altered development of neural progenitors without altered dynamics of the S-phase of the cell cycle. Pharmacol Biochem Behav 100:98–108

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Zlebnik NE, Anker JJ, Gliddon LA, Carroll ME (2010) Reduction of extinction and reinstatement of cocaine seeking by wheel running in female rats. Psychopharmacology 209:113–125

    Article  PubMed Central  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The study was supported by funds from the National Institute on Drug Abuse (DA022473 and DA034140 to CDM), National institute on Alcoholism and Alcohol Abuse (AA020098 and AA06420 to CDM) and Alcohol Beverage Medical Research Foundation to CDM. We appreciate the technical support of Elena Crawford for StereoInvestigator, and Robert Lintz, Ilham Polis and Yanabel Grant for assistance with intravenous self-administration studies. We thank Derrick Babb from the LSSI TSRI program and Mathew Soleiman from the independent study program at UCSD for assistance with immunohistochemistry. We thank Drs. Miranda Staples and Sucharita Somkuwar for critical reading of the manuscript. This is publication number 26041 from The Scripps Research Institute.

Author information

Authors and Affiliations

  1. Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 North Torrey Pines Road, SP30-2400, La Jolla, CA, 92037, USA

    Jeffery C. Sobieraj, Airee Kim, McKenzie J. Fannon & Chitra D. Mandyam

Authors
  1. Jeffery C. Sobieraj
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Airee Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. McKenzie J. Fannon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chitra D. Mandyam
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chitra D. Mandyam.

Additional information

J. C. Sobieraj and A. Kim have equal contribution.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sobieraj, J.C., Kim, A., Fannon, M.J. et al. Chronic wheel running-induced reduction of extinction and reinstatement of methamphetamine seeking in methamphetamine dependent rats is associated with reduced number of periaqueductal gray dopamine neurons. Brain Struct Funct 221, 261–276 (2016). https://doi.org/10.1007/s00429-014-0905-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00429-014-0905-7

Keywords

Search

Navigation