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Sex differences in neurobehavioral consequences of methamphetamine exposure in adult mice

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Abstract

Rationale

Recreational and medical use of stimulants is increasing, and their use may increase susceptibility to aging and promote neurobehavioral impairments. The long-term consequences of these psychostimulants and how they interact with age have not been fully studied.

Objectives

Our study investigated whether chronic exposure to the prototypical psychostimulant, methamphetamine (METH), at doses designed to emulate human therapeutic dosing, would confer a pro-oxidizing redox shift promoting long-lasting neurobehavioral impairments.

Methods

Groups of 4-month-old male and female C57BL/6 J mice were administered non-contingent intraperitoneal injections of either saline or METH (1.4 mg/kg) twice a day for 4 weeks. Mice were randomly assigned to one experimental group: (i) short-term cognitive assessments (at 5 months), (ii) long-term cognitive assessments (at 9.5 months), and (ii) longitudinal motor assessments (at 5, 7, and 9 months). Brain regions were assessed for oxidative stress and markers of neurotoxicity after behavior testing.

Results

Chronic METH exposure induced short-term effects on associative memory, gait speed, dopamine (DA) signaling, astrogliosis in females, and spatial learning and memory, balance, DA signaling, and excitotoxicity in males. There were no long-term effects of chronic METH on cognition; however, it decreased markers of excitotoxicity in the striatum and exacerbated age-associated motor impairments in males.

Conclusion

In conclusion, cognitive and motor functions were differentially and sex-dependently affected by METH exposure, and oxidative stress did not seem to play a role in the observed behavioral outcomes. Future studies are necessary to continue exploring the long-term neurobehavioral consequences of drug use in both sexes and the relationship between aging and drugs.

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References

  • Adriani W, Chiarotti F, Laviola G (1998) Elevated novelty seeking and peculiar d-amphetamine sensitization in periadolescent mice compared with adult mice. Behav Neurosci 112:1152–1166

    Article  CAS  PubMed  Google Scholar 

  • Andersen BB, Gundersen HJ, Pakkenberg B (2003) Aging of the human cerebellum: a stereological study. J Comp Neurol 466:356–365

    Article  PubMed  Google Scholar 

  • Ares-Santos S, Granado N, Espadas I, Martinez-Murillo R, Moratalla R (2014) Methamphetamine causes degeneration of dopamine cell bodies and terminals of the nigrostriatal pathway evidenced by silver staining. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology 39:1066–1080

  • Becker JB (1990) Estrogen rapidly potentiates amphetamine-induced striatal dopamine release and rotational behavior during microdialysis. Neurosci Lett 118:169–171

    Article  CAS  PubMed  Google Scholar 

  • Becker JB, Ming Hu (2008) Sex differences in drug abuse. Front Neuroendocrinol 29:36–47

    Article  CAS  PubMed  Google Scholar 

  • Becker JB, Ramirez VD (1981) Sex differences in the amphetamine stimulated release of catecholamines from rat striatal tissue in vitro. Brain Res 204:361–372

    Article  CAS  PubMed  Google Scholar 

  • Becker JB, Rudick CN (1999) Rapid effects of estrogen or progesterone on the amphetamine-induced increase in striatal dopamine are enhanced by estrogen priming: a microdialysis study. Pharmacol Biochem Behav 64:53–57

    Article  CAS  PubMed  Google Scholar 

  • Benson K, Flory K, Humphreys KL, Lee SS (2015) Misuse of stimulant medication among college students: a comprehensive review and meta-analysis. Clin Child Fam Psychol Rev 18:50–76

    Article  PubMed  Google Scholar 

  • Berman SB, Hastings TG (1999) Dopamine oxidation alters mitochondrial respiration and induces permeability transition in brain mitochondria. J Neurochem 73:1127–1137

    Article  CAS  PubMed  Google Scholar 

  • Bhatt SD, Dluzen DE (2005) Dopamine transporter function differences between male and female CD-1 mice. Brain Res 1035:188–195

    Article  CAS  PubMed  Google Scholar 

  • Bigdeli I, Asia MN, Miladi-Gorji H, Fadaei A (2015) The spatial learning and memory performance in methamphetamine-sensitized and withdrawn rats. Iran J Basic Med Sci 18:234–239

    PubMed  PubMed Central  Google Scholar 

  • Boileau I, McCluskey T, Tong J, Furukawa Y, Houle S, Kish SJ (2016) Rapid recovery of vesicular dopamine levels in methamphetamine users in early abstinence. Neuropsychopharmacology 41:1179–1187

    Article  CAS  PubMed  Google Scholar 

  • Buitelaar JK, Antoni Ramos-Quiroga J, Miguel Casas JJ, Kooij S, Niemelä A, Konofal E, Dejonckheere J, Challis BH, Medori R (2009) Safety and tolerability of flexible dosages of prolonged-release OROS methylphenidate in adults with attention-deficit/hyperactivity disorder. Neuropsychiatr Dis Treat 5:457–466

    CAS  PubMed  PubMed Central  Google Scholar 

  • Castner SA, Xiao L, Becker JB (1993) Sex differences in striatal dopamine: in vivo microdialysis and behavioral studies. Brain Res 610:127–134

    Article  CAS  PubMed  Google Scholar 

  • Chang L, Ernst T, Speck O, Patel H, DeSilva M, Leonido-Yee M, Miller EN (2002) Perfusion MRI and computerized cognitive test abnormalities in abstinent methamphetamine users. Psychiatry Research: Neuroimaging 114:65–79

    Article  PubMed  Google Scholar 

  • Cherner M, Suarez P, Casey C, Deiss R, Letendre S, Marcotte T, Florin Vaida J, Atkinson H, Grant I, Heaton RK (2010) Methamphetamine use parameters do not predict neuropsychological impairment in currently abstinent dependent adults. Drug Alcohol Depend 106:154–163

    Article  PubMed  Google Scholar 

  • Clarke LE, Liddelow SA, Chakraborty C, Münch AE, Heiman M, Barres BA (2018) Normal aging induces A1-like astrocyte reactivity. Proc Natl Acad Sci 115:E1896

    CAS  PubMed  PubMed Central  Google Scholar 

  • D’Arcy C, Luevano JE, Miranda-Arango M, Pipkin JA, Jackson JA, Castañeda E, Gosselink KL, O’Dell LE (2016) Extended access to methamphetamine self-administration up-regulates dopamine transporter levels 72hours after withdrawal in rats. Behav Brain Res 296:125–128

    Article  PubMed  CAS  Google Scholar 

  • da-Rosa DD, Valvassori SS, Steckert AV, Arent CO, Ferreira CL, Lopes-Borges J, Varela RB, Mariot E, Dal-Pizzol F, Andersen ML, Quevedo J (2012) Differences between dextroamphetamine and methamphetamine: behavioral changes and oxidative damage in brain of Wistar rats, J Neural Transm (Vienna), 119: 31-8.

  • de Fiebre NC, Sumien N, Forster MJ, de Fiebre CM (2006) Spatial learning and psychomotor performance of C57BL/6 mice: age sensitivity and reliability of individual differences. Age (dordr) 28:235–253

    Article  Google Scholar 

  • Dluzen DE, Bhatt S, McDermott JL (2008) Differences in reserpine-induced striatal dopamine output and content between female and male mice: implications for sex differences in vesicular monoamine transporter 2 function. Neuroscience 154:1488–1496

    Article  CAS  PubMed  Google Scholar 

  • Dubey A, Forster MJ, Lal H, Sohal RS (1996) Effect of age and caloric intake on protein oxidation in different brain regions and on behavioral functions of the mouse. Arch Biochem Biophys 333:189–197

    Article  CAS  PubMed  Google Scholar 

  • Fattore L, Altea S, Fratta W (2008) Sex differences in drug addiction: a review of animal and human studies. Womens Health (lond) 4:51–65

    Article  CAS  Google Scholar 

  • Filograna R, Koolmeister C, Upadhyay M, Pajak A, Clemente P, Wibom R, Simard ML, Wredenberg A, Freyer C, Stewart JB, Larsson NG (2019) Modulation of mtDNA copy number ameliorates the pathological consequences of a heteroplasmic mtDNA mutation in the mouse. Science Advances 5:eaav9824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Filograna R, Mennuni M, Alsina D, Larsson N-G (2021) Mitochondrial DNA copy number in human disease: the more the better? FEBS Lett 595:976–1002

    Article  CAS  PubMed  Google Scholar 

  • Fitzmaurice PS, Tong J, Yazdanpanah M, Liu PP, Kalasinsky KS, Kish SJ (2006) Levels of 4-hydroxynonenal and malondialdehyde are increased in brain of human chronic users of methamphetamine. J Pharmacol Exp Ther 319:703–709

    Article  CAS  PubMed  Google Scholar 

  • Flora G, Lee YW, Nath A, Maragos W, Hennig B, Toborek M (2002) Methamphetamine-induced TNF-alpha gene expression and activation of AP-1 in discrete regions of mouse brain: potential role of reactive oxygen intermediates and lipid peroxidation. Neuromolecular Med 2:71–85

    Article  CAS  PubMed  Google Scholar 

  • Frey BN, Valvassori SS, Réus GZ, Martins MR, Petronilho FC, Bardini K, Dal-Pizzol F, Kapczinski F, Quevedo J (2006) Changes in antioxidant defense enzymes after d-amphetamine exposure: implications as an animal model of mania. Neurochem Res 31:699–703

    Article  CAS  PubMed  Google Scholar 

  • Friedman SD, Castañeda E, Hodge GK (1998) Long-term monoamine depletion, differential recovery, and subtle behavioral impairment following methamphetamine-induced neurotoxicity. Pharmacol Biochem Behav 61:35–44

    Article  CAS  PubMed  Google Scholar 

  • Friend DM, Keefe KA (2013) Glial reactivity in resistance to methamphetamine-induced neurotoxicity. J Neurochem 125:566–574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gasiorowska A, Wydrych M, Drapich P, Zadrozny M, Steczkowska M, Niewiadomski W, Niewiadomska G (2021) The biology and pathobiology of glutamatergic, cholinergic, and dopaminergic signaling in the aging brain, Front Aging Neurosci, 13.

  • Goodman DW, Ginsberg L, Weisler RH, Cutler AJ, Hodgkins P (2005) An interim analysis of the quality of life, effectiveness, safety, and tolerability (QU.E.S.T.) evaluation of mixed amphetamine salts extended release in adults with ADHD. CNS Spectr 10:26–34

    Article  PubMed  Google Scholar 

  • Graham DG (1978) Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol Pharmacol 14:633–643

    CAS  PubMed  Google Scholar 

  • Granado N, Ares-Santos S, O’Shea E, Carlos Vicario-Abejón M, Colado I, Moratalla R (2010) Selective vulnerability in striosomes and in the nigrostriatal dopaminergic pathway after methamphetamine administration. Neurotox Res 18:48–58

    Article  PubMed  Google Scholar 

  • Halpin LE, Collins SA, Yamamoto BK (2014) Neurotoxicity of methamphetamine and 3,4-methylenedioxymethamphetamine. Life Sci 97:37–44

    Article  CAS  PubMed  Google Scholar 

  • Harold C, Wallace T, Friedman R, Gudelsky G, Yamamoto B (2000) Methamphetamine selectively alters brain glutathione. Eur J Pharmacol 400:99–102

    Article  CAS  PubMed  Google Scholar 

  • He L-Q, Jia-hong Lu, Yue Z-y (2013) Autophagy in ageing and ageing-associated diseases. Acta Pharmacol Sin 34:605–611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hirata H, Asanuma M, Cadet JL (1998) Melatonin attenuates methamphetamine-induced toxic effects on dopamine and serotonin terminals in mouse brain. Synapse 30:150–155

    Article  CAS  PubMed  Google Scholar 

  • Hotchkiss AJ, Gibb JW (1980) Long-term effects of multiple doses of methamphetamine on tryptophan hydroxylase and tyrosine hydroxylase activity in rat brain. J Pharmacol Exp Ther 214:257–262

    CAS  PubMed  Google Scholar 

  • Huang M-C, Lin S-K, Chen C-H, Pan C-H, Lee C-H, Liu H-C (2013) Oxidative stress status in recently abstinent methamphetamine abusers. Psychiatry Clin Neurosci 67:92–100

    Article  CAS  PubMed  Google Scholar 

  • Huang Y-N, Yang L-Y, Wang J-Y, Lai C-C, Chiu C-T, Wang J-Y (2017) L-ascorbate protects against methamphetamine-induced neurotoxicity of cortical cells via inhibiting oxidative stress, autophagy, and apoptosis. Mol Neurobiol 54:125–136

    Article  CAS  PubMed  Google Scholar 

  • Ilieva I, Boland J, Farah MJ (2013) Objective and subjective cognitive enhancing effects of mixed amphetamine salts in healthy people. Neuropharmacology 64:496–505

    Article  CAS  PubMed  Google Scholar 

  • Johnston, L. D., R. A. Miech, P. M. O’Malley, J. G. Bachman, J. E. Schulenberg, and M. E. Patrick. 2020. Monitoring the future national survey results on drug use 1975–2019: Overview, key findings on adolescent drug use. In. Ann Arbor: Institute for Social Research, University of Michigan.

  • Jones MJ, Goodman SJ, Kobor MS (2015) DNA methylation and healthy human aging. Aging Cell 14:924–932

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaasinen V, Rinne JO (2002) Functional imaging studies of dopamine system and cognition in normal aging and Parkinson’s disease. Neurosci Biobehav Rev 26:785–793

    Article  CAS  PubMed  Google Scholar 

  • Kamei H, Nagai T, Nakano H, Togan Y, Takayanagi M, Takahashi K, Kobayashi K, Yoshida S, Maeda K, Takuma K, Nabeshima T, Yamada K (2006) Repeated methamphetamine treatment impairs recognition memory through a failure of novelty-induced ERK1/2 activation in the prefrontal cortex of mice. Biol Psychiatry 59:75–84

    Article  CAS  PubMed  Google Scholar 

  • LeBlanc-Duchin D, Taukulis HK (2009) Chronic oral methylphenidate induces post-treatment impairment in recognition and spatial memory in adult rats. Neurobiol Learn Mem 91:218–225

    Article  CAS  PubMed  Google Scholar 

  • Martins MR, Reinke A, Petronilho FC, Gomes KM, Dal-Pizzol F, Quevedo J (2006) Methylphenidate treatment induces oxidative stress in young rat brain. Brain Res 1078:189–197

    Article  CAS  PubMed  Google Scholar 

  • McCann UD, Kuwabara H, Kumar A, Palermo M, Abbey R, Brasic J, Ye W, Alexander M, Dannals RF, Wong DF, Ricaurte GA (2008) Persistent cognitive and dopamine transporter deficits in abstinent methamphetamine users. Synapse 62:91–100

    Article  CAS  PubMed  Google Scholar 

  • McDonnell-Dowling K, Kelly JP (2017) The role of oxidative stress in methamphetamine-induced toxicity and sources of variation in the design of animal studies. Curr Neuropharmacol 15:300–314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Melega WP, Quintana J, Raleigh MJ, Stout DB, Dan-Chu Yu, Lin K-P, Huang S-C, Phelps ME (1996) 6-[18F]fluoro-L-DOPA-PETstudies show partial reversibility of long-term effects of chronic amphetamine in monkeys. Synapse 22:63–69

    Article  CAS  PubMed  Google Scholar 

  • Meng X, Chenghong Zhang Yu, Guo YH, Wang C, Chu H, Kong Li, Ma H (2020) TBHQ attenuates neurotoxicity induced by methamphetamine in the VTA through the Nrf2/HO-1 and PI3K/AKT signaling pathways. Oxid Med Cell Longev 2020:8787156

    PubMed  PubMed Central  Google Scholar 

  • Milesi-Hallé A, Hendrickson HP, Laurenzana EM, Gentry WB, Owens SM (2005) Sex- and dose-dependency in the pharmacokinetics and pharmacodynamics of (+)-methamphetamine and its metabolite (+)-amphetamine in rats. Toxicol Appl Pharmacol 209:203–213

    Article  PubMed  CAS  Google Scholar 

  • Milesi-Hallé A, McMillan DE, Laurenzana EM, Byrnes-Blake KA, Owens SM (2007) Sex differences in (+)-amphetamine- and (+)-methamphetamine-induced behavioral response in male and female Sprague-Dawley rats. Pharmacol Biochem Behav 86:140–149

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Moszczynska A, Fitzmaurice P, Ang L, Kalasinsky KS, Peretti FJ, Aiken SS, Wickham DJ, Sherwin A, Nobrega JN, Forman HJ, Kish SJ (2004) Brain antioxidant systems in human methamphetamine users. J Neurochem 89:1396–1408

    Article  CAS  Google Scholar 

  • Nichols NR, Day JR, Laping NJ, Johnson SA, Finch CE (1993) GFAP mRNA increases with age in rat and human brain. Neurobiol Aging 14:421–429

    Article  CAS  PubMed  Google Scholar 

  • Pathak G, Ibrahim BA, McCarthy SA, Baker K, Kelly MP (2015) Amphetamine sensitization in mice is sufficient to produce both manic- and depressive-related behaviors as well as changes in the functional connectivity of corticolimbic structures. Neuropharmacology 95:434–447

    Article  CAS  PubMed  Google Scholar 

  • Pyle A, Anugrha H, Kurzawa-Akanbi M, Yarnall A, Burn D, Hudson G (2016) Reduced mitochondrial DNA copy number is a biomarker of Parkinson’s disease. Neurobiol Aging 38:216.e7–16.e10

    Article  CAS  Google Scholar 

  • Quiros PM, Goyal A, Jha P, Auwerx J (2017) Analysis of mtDNA/nDNA ratio in mice. Curr Protoc Mouse Biol 7:47–54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reagan-Shaw S, Nihal M, Ahmad N (2008) Dose translation from animal to human studies revisited. Faseb j 22:659–661

    Article  CAS  PubMed  Google Scholar 

  • Rebrin I, Forster MJ, Sohal RS (2007) Effects of age and caloric intake on glutathione redox state in different brain regions of C57BL/6 and DBA/2 mice. Brain Res 1127:10–18

    Article  CAS  PubMed  Google Scholar 

  • Repantis D, Schlattmann P, Laisney O, Heuser I (2010) Modafinil and methylphenidate for neuroenhancement in healthy individuals: a systematic review. Pharmacol Res 62:187–206

    Article  CAS  PubMed  Google Scholar 

  • Ricaurte GA, Guillery RW, Seiden LS, Schuster CR (1984) Nerve terminal degeneration after a single injection of D-amphetamine in iprindole-treated rats: relation to selective long-lasting dopamine depletion. Brain Res 291:378–382

    Article  CAS  PubMed  Google Scholar 

  • Saatman KE, Creed J, Raghupathi R (2010) Calpain as a therapeutic target in traumatic brain injury. Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics 7:31–42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • SAMHSA (2019) Key substance use and mental health indicators in the United States: results from the 2018 National Survey on Drug Use and Health. In. Rockville, MD: Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration.

  • Shaerzadeh F, Streit WJ, Heysieattalab S, Khoshbouei H (2018) Methamphetamine neurotoxicity, microglia, and neuroinflammation. J Neuroinflammation 15:341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shams WM, Sanio C, Quinlan MG, Brake WG (2016) 17β-Estradiol infusions into the dorsal striatum rapidly increase dorsal striatal dopamine release in vivo. Neuroscience 330:162–170

    Article  CAS  PubMed  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  CAS  PubMed  Google Scholar 

  • Shoji H, Takao K, Hattori S, Miyakawa T (2016) Age-related changes in behavior in C57BL/6J mice from young adulthood to middle age. Mol Brain 9:11

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Simpson J, Ryan C, Curley A, Mulcaire J, Kelly JP (2012) Sex differences in baseline and drug-induced behavioural responses in classical behavioural tests. Prog Neuropsychopharmacol Biol Psychiatry 37:227–236

    Article  CAS  PubMed  Google Scholar 

  • Slivka A, Cohen G (1985) Hydroxyl radical attack on dopamine. J Biol Chem 260:15466–15472

    Article  CAS  PubMed  Google Scholar 

  • Spencer TJ, Adler LA, McGough JJ, Muniz R, Jiang H, Pestreich L (2007) Efficacy and safety of dexmethylphenidate extended-release capsules in adults with attention-deficit/hyperactivity disorder. Biol Psychiat 61:1380–1387

    Article  CAS  PubMed  Google Scholar 

  • Stokes AH, Hastings TG, Vrana KE (1999) Cytotoxic and genotoxic potential of dopamine. J Neurosci Res 55:659–665

    Article  CAS  PubMed  Google Scholar 

  • Sumien N, Sims MN, Taylor HJ, Forster MJ (2006) Profiling psychomotor and cognitive aging in four-way cross mice. Age (dordr) 28:265–282

    Article  Google Scholar 

  • Sumien N, Heinrich KR, Shetty RA, Sohal RS, Forster MJ (2009) Prolonged intake of coenzyme Q10 impairs cognitive functions in mice. J Nutr 139:1926–1932

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • UN ODC (United Nations Office on Drugs and Crime) (2021) World drug report. https://www.unodc.org/unodc/en/data-and-analysis/wdr2021.html

  • Vanaveski T, Narvik J, Innos J, Philips M-A, Ottas A, Plaas M, Haring L, Zilmer M, Vasar E (2018) Repeated administration of D-amphetamine induces distinct alterations in behavior and metabolite levels in 129Sv and Bl6 mouse strains, Frontiers in Neuroscience, 12.

  • Volkow ND, Wang GJ, Smith L, Fowler JS, Telang F, Logan J, Tomasi D (2015) Recovery of dopamine transporters with methamphetamine detoxification is not linked to changes in dopamine release. Neuroimage 121:20–28

    Article  CAS  PubMed  Google Scholar 

  • Walker QD, Rooney MB, Wightman RM, Kuhn CM (2000) Dopamine release and uptake are greater in female than male rat striatum as measured by fast cyclic voltammetry. Neuroscience 95:1061–1070

    Article  CAS  PubMed  Google Scholar 

  • Wallace TL, Gudelsky GA, Vorhees CV (1999) Methamphetamine-induced neurotoxicity alters locomotor activity, stereotypic behavior, and stimulated dopamine release in the rat. J Neurosci 19:9141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang J, Sareddy GR, Yujiao Lu, Pratap UP, Tang F, Greene KM, Meyre PL, Tekmal RR, Vadlamudi RK, Brann DW (2020) Astrocyte-derived estrogen regulates reactive astrogliosis and is neuroprotective following ischemic brain injury. J Neurosci 40:9751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang GJ, Smith L, Volkow N, Telang F, Logan J, Wong C, Hoffman W, Pradhan K, Fowler JS, Thanos P (2009) Recovery of dopamine transporter loss after protracted abstinence in methamphetamine users. In.: Soc Nuclear Med.

  • Weyandt LL, Oster DR, Marraccini ME, Gudmundsdottir BG, Munro BA, Rathkey ES, McCallum A (2016) Prescription stimulant medication misuse: where are we and where do we go from here? Exp Clin Psychopharmacol 24:400–414

    Article  PubMed  PubMed Central  Google Scholar 

  • Weyandt LL, White TL, Gudmundsdottir BG, Nitenson AZ, Rathkey ES, De Leon KA, Bjorn SA (2018) Neurocognitive, autonomic, and mood effects of adderall: a pilot study of healthy college students. Pharmacy (basel, Switzerland) 6:58

    Google Scholar 

  • Wilens TE, Carrellas NW, Martelon MaryKate, Yule AM, Fried R, Anselmo R, McCabe SE (2017) Neuropsychological functioning in college students who misuse prescription stimulants. Am J Addict 26:379–387

    Article  PubMed  PubMed Central  Google Scholar 

  • Wilson JM, Kalasinsky KS, Levey AI, Bergeron C, Reiber G, Anthony RM, Schmunk GA, Shannak K, Haycock JW, Kish SJ (1996) Striatal dopamine nerve terminal markers in human, chronic methamphetamine users. Nat Med 2:699–703

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto BK, Raudensky J (2008) The role of oxidative stress, metabolic compromise, and inflammation in neuronal injury produced by amphetamine-related drugs of abuse. J Neuroimmune Pharmacol 3:203–217

    Article  PubMed  PubMed Central  Google Scholar 

  • Yan X-X, Jeromin A, Jeromin A (2012) Spectrin breakdown products (SBDPs) as potential biomarkers for neurodegenerative diseases. Curr Transl Geriatr Exp Gerontol Rep 1:85–93

  • Yanai S, Endo S (2021) Functional aging in male C57BL/6J mice across the life-span: a systematic behavioral analysis of motor, emotional, and memory function to define an aging phenotype, Front Aging Neurosci, 13.

  • Yu Y, Feng L, Li J, Lan X, L. A, Lv X, Zhang M, Chen L (2017) The alteration of autophagy and apoptosis in the hippocampus of rats with natural aging-dependent cognitive deficits, Behav Brain Res, 334: 155-62.

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This work was supported by National Institutes of Health/National Institute on Aging T32 AG020494 and a seed grant from University of North Texas Health Science Center Research Office.

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Davis, D.L., Metzger, D.B., Vann, P.H. et al. Sex differences in neurobehavioral consequences of methamphetamine exposure in adult mice. Psychopharmacology 239, 2331–2349 (2022). https://doi.org/10.1007/s00213-022-06122-8

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