Abstract
Methamphetamine (mAMPH) is an addictive drug that produces memory and recall impairments in humans. Animals subjected to a binge mAMPH dosing regimen that damages brain dopamine and serotonin terminals show impairments in an object recognition (OR) task. Earlier research demonstrated that preceding a single-day mAMPH binge regimen with several days of increasing mAMPH doses greatly attenuates its neurotoxicity in rats. The escalating dose (ED) paradigm appears to mimic the human pattern of escalating drug intake. The current aim was to test whether an ED plus binge mAMPH regimen produces OR impairments. In addition to its translational value, this experiment helps address whether monoaminergic neurotoxicity accounts for OR impairments seen after mAMPH administration. To further address this issue, a separate experiment investigated both OR impairments and monoamine transporter integrity in groups of rats treated with a range of mAMPH doses during a single day. An ED mAMPH regimen attenuated the acute hyperthermic response to the subsequent mAMPH binge and prevented the OR impairments and reductions in [125I]RTI-55 binding to monoamine transporters in striatum, hippocampus (HC), and perirhinal cortex (pRh) that otherwise occur 1 week after the mAMPH binge. Single-day mAMPH regimens (4 × 1mg/kg to 4 × 4 mg/kg, s.c.) dose-dependently produced acute hyperthermia and, 1 week post-mAMPH, produced dose-dependent impairments in OR and reductions in monoamine transporter binding. The OR impairments of single-day mAMPH-treated rats correlated with monoaminergic transporter loss in ventral caudate-putamen, HC, and pRh. In aggregate, these findings suggest a correspondence between mAMPH-induced monoaminergic injury and the resulting OR deficits.
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References
Axt KJ, Molliver ME (1991). Immunocytochemical evidence for methamphetamine-induced serotonergic axon loss in the rat brain. Synapse 9: 302–313.
Badiani A, Robinson TE (2004). Drug-induced neurobehavioral plasticity: the role of environmental context. Behav Pharmacol 15: 327–339.
Belcher AM, O'Dell SJ, Marshall JF (2005). Impaired object recognition memory following methamphetamine, but not p-chloroamphetamine- or d-amphetamine-induced neurotoxicity. Neuropsychopharmacology 30: 2026–2034.
Belcher AM, O'Dell SJ, Marshall JF (2006). A sensitizing regimen of methamphetamine causes impairments in a novelty preference task of object recognition. Behav Brain Res 170: 167–172.
Bisagno V, Ferguson D, Luine VN (2002). Short toxic methamphetamine schedule impairs object recognition task in male rats. Brain Res 940: 95–101.
Bisagno V, Ferguson D, Luine VN (2003). Chronic D-amphetamine induces sexually dimorphic effects on locomotion, recognition memory, and brain monoamines. Pharmacol Biochem Behav 74: 859–867.
Boja JW, Mitchell WM, Patel A, Kopajtic TA, Carroll FI, Lewin AH et al (1992). High-affinity binding of [125I]RTI-55 to dopamine and serotonin transporters in rat brain. Synapse 12: 27–36.
Bowyer JF, Davies DL, Schmued L, Broening HW, Newport GD, Slikker Jr W et al (1994). Further studies of the role of hyperthermia in methamphetamine neurotoxicity. J Pharmacol Exp Ther 268: 1571–1580.
Bowyer JF, Tank AW, Newport GD, Slikker Jr W, Ali SF, Holson RR (1992). The influence of environmental temperature on the transient effects of methamphetamine on dopamine levels and dopamine release in rat striatum. J Pharmacol Exp Ther 260: 817–824.
Briand LA, Robinson TE, Maren S (2005). Enhancement of auditory fear conditioning after housing in a complex environment is attenuated by prior treatment with amphetamine. Learn Mem 12: 553–556.
Broadbent NJ, Squire LR, Clark RE (2004). Spatial memory, recognition memory, and the hippocampus. Proc Natl Acad Sci USA 101: 14515–14520.
Brown MW, Aggleton JP (2001). Recognition memory: what are the roles of the perirhinal cortex and hippocampus? Nat Rev Neurosci 2: 51–61.
Brownstein MJ, Palkovits M (1984). Catecholamines, serotonin, acetylcholine and γ-aminobutyric acid in the rat brain: biochemical studies. In: Björklund A, Hökfelt T (eds). Handbook of Chemical Neuroanatomy. Elsevier: New York. pp 23–54.
Chapman DE, Hanson GR, Kesner RP, Keefe KA (2001). Long-term changes in basal ganglia function after a neurotoxic regimen of methamphetamine. J Pharmacol Exp Ther 296: 520–527.
Clark RE, Zola SM, Squire LR (2000). Impaired recognition memory in rats after damage to the hippocampus. J Neurosci 20: 8853–8860.
Commins DL, Seiden LS (1986). alpha-Methyltyrosine blocks methylamphetamine-induced degeneration in the rat somatosensory cortex. Brain Res 365: 15–20.
Donnan GA, Kaczmarczyk SJ, McKenzie JS, Kalnins RM, Chilco PJ, Mendelsohn FA (1989). Catecholamine uptake sites in mouse brain: distribution determined by quantitative [3H]mazindol autoradiography. Brain Res 504: 64–71.
Eisch AJ, Gaffney M, Weihmuller FB, O'Dell SJ, Marshall JF (1992). Striatal subregions are differentially vulnerable to the neurotoxic effects of methamphetamine. Brain Res 598: 321–326.
Eisch AJ, O'Dell SJ, Marshall JF (1996). Striatal and cortical NMDA receptors are altered by a neurotoxic regimen of methamphetamine. Synapse 22: 217–225.
Ellison G, Eison MS, Huberman HS, Daniel F (1978). Long-term changes in dopaminergic innervation of caudate nucleus after continuous amphetamine administration. Science 201: 276–278.
Ennaceur A, Aggleton JP (1997). The effects of neurotoxic lesions of the perirhinal cortex combined to fornix transection on object recognition memory in the rat. Behav Brain Res 88: 181–193.
Ennaceur A, Delacour J (1988). A new one-trial test for neurobiological studies of memory in rats. 1: behavioral data. Behav Brain Res 31: 47–59.
Friedman SD, Castaneda E, Hodge GK (1998). Long-term monoamine depletion, differential recovery, and subtle behavioral impairment following methamphetamine-induced neurotoxicity. Pharmacol Biochem Behav 61: 35–44.
Gibb JW, Kogan FJ (1979). Influence of dopamine synthesis on methamphetamine-induced changes in striatal and adrenal tyrosine hydroxylase activity. Naunyn Schmiedebergs Arch Pharmacol 310: 185–187.
Gonzalez R, Rippeth JD, Carey CL, Heaton RK, Moore DJ, Schweinsburg BC et al (2004). Neurocognitive performance of methamphetamine users discordant for history of marijuana exposure. Drug and Alcohol Dependence 76: 181–190.
He J, Yang Y, Yu Y, Li X, Li X-M (2006). The effects of chronic administration of quetiapine on the methamphetamine-induced recognition memory impairment and dopaminergic terminal deficit in rats. Behav Brain Res 172: 39–45.
Heldt SA, Stanek L, Chhatwal JP, Ressler KJ (2007). Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memories. Mol Psychiatry 12: 656–670.
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.
Hotchkiss AJ, Morgan ME, Gibb JW (1979). The long-term effects of multiple doses of methamphetamine on neostriatal tryptophan hydroxylase, tyrosine hydroxylase, choline acetyltransferase and glutamate decarboxylase activities. Life Sci 25: 1373–1378.
Itzhak Y, Martin JL, Ali SF (2002). Methamphetamine-induced dopaminergic neurotoxicity in mice: Long-lasting sensitization to the locomotor stimulation and desensitization to the rewarding effects of methamphetamine. Prog NeuroPsychopharmacol Biol Psychiatry 26: 1177–1183.
Kelly A, Laroche S, Davis S (2003). Activation of mitogen-activated protein kinase/extracellular signal-regulated kinase in hippocampal circuitry is required for consolidation and reconsolidation of recognition memory. J Neurosci 23: 5354–5360.
Koda LY, Gibb JW (1973). Adrenal and striatal tyrosine hydroxylase activity after methamphetamine. J Pharmacol Exp Ther 185: 42–48.
Kolb B, Gorny G, Li Y, Samaha AN, Robinson TE (2003). Amphetamine or cocaine limits the ability of later experience to promote structural plasticity in the neocortex and nucleus accumbens. Proc Nalt Acad Sci USA 100: 10523–10528.
Lavoie MJ, Hastings TG (1999). Dopamine quinone formation and protein modification associated with the striatal neurotoxicity of methamphetamine: evidence against a role for extracellular dopamine. J Neurosci 19: 1484–1491.
Mark KA, Soghomonian JJ, Yamamoto BK (2004). High-dose methamphetamine acutely activates the striatonigral pathway to increase striatal glutamate and mediate long-term dopamine toxicity. J Neurosci 24: 11449–11456.
Meunier M, Bachevalier J, Mishkin M, Murray EA (1993). Effects on visual recognition of combined and separate ablations of the entorhinal and perirhinal cortex in rhesus monkeys. J Neurosci 13: 5418–5432.
Mumby DG, Gaskin S, Glenn MJ, Schramek TE, Lehmann H (2002). Hippocampal damage and exploratory preferences in rats: memory for objects, places, and contexts. Learn Mem 9: 49–57.
Nordahl TE, Salo R, Leamon M (2003). High-dose methamphetamine acutely activates the striatonigral pathway to increase striatal glutamate and mediate long-term dopamine toxicity. J Neurosci 24: 11449–11456.
O'Neil ML, Kuczenski R, Segal DS, Cho AK, Lacan G, Melega WP (2006). Escalating dose pretreatment induces pharmacodynamic and not pharmacokinetic tolerance to a subsequent high-dose methamphetamine binge. Synapse 60: 465–473.
O'Dell SJ, Marshall JF (2000). Repeated administration of methamphetamine damages cells in the somatosensory cortex: overlap with cytochrome oxidase-rich barrels. Synapse 37: 32–37.
Ornstein TJ, Iddon JL, Baldacchino AM, Sahakian BJ, London M, Everitt BJ . et al (2000). Profiles of cognitive dysfunction in chronic amphetamine and heroin abusers. Neuropsychopharmacology 23: 113–126.
Paulus MP, Hozack NE, Zauscher BE, Frank L, Brown CG, Braff DL et al (2002). Behavioral and functional neuroimaging evidence for prefrontal dysfunction in methamphetamine-dependent subjects. Neuropsychopharmacology 26: 53–63.
Paxinos G, Watson C (1998). The Rat Brain in Stereotaxic Coordinates. Academic Press: San Diego.
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.
Ricaurte GA, Schuster CR, Seiden LS (1980). Long-term effects of repeated methylamphetamine administration on dopamine and serotonin neurons in the rat brain: a regional study. Brain Res 193: 153–163.
Richtand NM, Kelsoe JR, Segal DS, Kuczenski R (1995). Regional quantification of dopamine transporter mRNA in rat brain using a ribonuclease protection assay. Neurosci Lett 200: 73–76.
Rogers RD, Everitt BJ, Baldacchino A, Blackshaw AJ, Swainson R, Wynne K et al (1999). Dissociable deficits in the decision-making cognition of chronic amphetamine abusers, opiate abusers, patients with focal damage to prefrontal cortex, and tryptophan-depleted normal volunteers: evidence for monoaminergic mechanisms. Neuropsychopharmacology 20: 322–339.
Salo R, Nordahl TE, Possin K, Leamon M, Gibson DR, Galloway GP et al (2002). Preliminary evidence of reduced cognitive inhibition in methamphetamine-dependent individuals. Psychiatry Res 111: 65–74.
Schmidt CJ, Ritter JK, Sonsalla PK, Hanson GR, Gibb JW (1985). Role of dopamine in the neurotoxic effects of methamphetamine. J Pharmacol Exp Ther 233: 539–544.
Schröder N, O'Dell SJ, Marshall JF (2003). Neurotoxic methamphetamine regimen severely impairs recognition memory in rats. Synapse 49: 89–96.
Segal DS, Kuczenski R, O'Neil ML, Melega WP, Cho AK (2003). Escalating dose methamphetamine pretreatment alters the behavioral and neurochemical profiles associated with exposure to a high-dose methamphetamine binge. Neuropsychopharmacology 28: 1730–1740.
Seiden LS, MacPhail RC, Oglesby MW (1975). Catecholamines and drug-behavior interactions. Fed Proc 34: 1823–1831.
Simon SL, Domier CP, Sim T, Richardson K, Rawson RA, Ling W (2002). Cognitive performance of current methamphetamine and cocaine abusers. J Addict Disord 21: 61–74.
Sim T, Simon SL, Domier CP, Richardson K, Rawson RA, Ling W (2002). Cognitive deficits among methamphetamine users with attention deficit hyperactivity disorder symptomatology. J Addict Dis 21: 75–89.
Squire LR, Zola-Morgan S (1991). The medial temporal lobe memory system. Science 253: 1380–1386.
Thompson PM, Hayashi KM, Simon SL, Geaga JA, Hong MS, Sui Y et al (2004). Structural abnormalities in the brains of human subjects who use methamphetamine. J Neurosci 24: 6028–6036.
Tohyama M, Takatsuji K (1998). Atlas of Neuroactive Substances and Their Receptors in the Rat. Oxford University Press: New York, NY.
Turchi J, Saunders RC, Mishkin M (2005). Effects of cholinergic deafferentation of the rhinal cortex on visual recognition memory in monkeys. Proc Natl Acad Sci USA 102: 2158–2161.
Volkow ND, Chang L, Wang GJ, Fowler JS, Leonido-Yee M, Franceschi D et al (2001). Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers. Am J Psychiatry 158: 377–382.
Wagner GC, Seiden LS, Schuster CR (1979). Methamphetamine-induced changes in brain catecholamines in rats and guinea pigs. Drug and Alcohol Dependence 4: 435–438.
Walsh SL, Wagner GC (1992). Motor impairments after methamphetamine-induced neurotoxicity in the rat. J Pharmacol Exp Ther 263: 617–626.
Wang GJ, Volkow ND, Chang L, Miller E, Sedler M, Hitzemann R et al (2004). Preliminary evidence of reduced cognitive inhibition in methamphetamine-dependent individuals. Am J Psychiatry 161: 242–248.
Warburton EC, Glover CP, Massey PV, Wan H, Johnson B, Bienemann A et al (2005). cAMP responsive element-binding protein phosphorylation is necessary for perirhinal long-term potentiation and recognition memory. J Neurosci 25: 6296–6303.
Winters BD, Bussey TJ (2005). Glutamate receptors in perirhinal cortex mediate encoding, retrieval, and consolidation of object recognition memory. J Neurosci 25: 4243–4251.
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This work was supported by PHS awards DA-12204 and DA-4-8849.
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Belcher, A., Feinstein, E., O'Dell, S. et al. Methamphetamine Influences on Recognition Memory: Comparison of Escalating and Single-Day Dosing Regimens. Neuropsychopharmacol 33, 1453–1463 (2008). https://doi.org/10.1038/sj.npp.1301510
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DOI: https://doi.org/10.1038/sj.npp.1301510
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