Abstract
Methamphetamine (METH) is a psychostimulant drug with potent effects on the central nervous system that can cause psychotic symptoms similar to those of schizophrenia. Specific alterations in GABAergic neuronal markers have been reported in schizophrenia and animal models of psychotic illness. The aim of this study was to determine whether there are changes in subpopulations of GABAergic neurons, defined by the presence of calcium binding proteins (CBPs), in animal models of METH abuse. Rats received acute (Binge) doses of 4 × 6 mg/kg, a chronic escalating dose regime (0.1–4 mg/kg over 14 days) or a combination of the two and were compared with a vehicle-administered control group. Brains were taken and sections of frontal cortex (Cg1) and hippocampus (dentate gyrus and CA1-3 regions) underwent immunostaining for three CBPs [parvalbumin (PV), calbindin (CB), and calretinin (CR)]. Significant decreases in PV-immunoreactive (IR) neurons in each METH group and all regions were observed. Smaller METH-induced deficits in CB–IR cells were observed, reaching significance primarily following chronic METH regimes, while CR–IR was significantly reduced only in frontal cortex following chronic administration. These results suggest that METH regimes in rats can induce selective deficits in GABAergic neuronal subtypes similar to those seen in schizophrenia and may underlie the psychosis and/or cognitive impairment that can occur in METH abuse and dependence.
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References
Açikgöz O, Gönenç S, Gezer S, Kayatekin BM, Uysal N, Semin I, Gure A (2001) Methamphetamine causes depletion of glutathione and an increase in oxidized glutathione in the rat striatum and prefrontal cortex. Neurotox Res 3:277–280
Armstrong BD, Noguchi KK (2004) The neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine on serotonin, dopamine, and GABA-ergic terminals: an in-vitro autoradiographic study in rats. Neurotoxicology 25:905–914
Beasley CL, Reynolds GP (1997) Parvalbumin-immunoreactive neurons are reduced in the prefrontal cortex of schizophrenics. Schizophr Res 24:349–355
Beasley CL, Zhang ZJ, Patten I, Reynolds GP (2002) Selective deficits in prefrontal cortex GABAergic neurons in schizophrenia defined by the presence of calcium-binding proteins. Biol Psychiatry 52:708–715
Benes FM, Berretta S (2001) GABAergic interneurons: implications for understanding schizophrenia and bipolar disorder. Neuropsychopharmacology 25:1–27
Braun I, Genius J, Grunze H, Bender A, Möller HJ, Rujescu D (2007) Alterations of hippocampal and prefrontal GABAergic interneurons in an animal model of psychosis induced by NMDA receptor antagonism. Schizophr Res 97:254–263
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
Glasner-Edwards S, Mooney LJ (2014) Methamphetamine psychosis: epidemiology and management. CNS Drugs 28:1115–1126
Harte MK, Powell SB, Swerdlow NR, Geyer MA, Reynolds GP (2007) Deficits in parvalbumin and calbindin immunoreactive cells in the hippocampus of isolation reared rats. J Neural Transm 114:893–898
Hsieh JH, Stein DJ, Howells FM (2014) The neurobiology of methamphetamine induced psychosis. Front Hum Neurosci 8:537
Jenkins TA, Harte MK, McKibben CE, Elliott JJ, Reynolds GP (2008) Disturbances in social interaction occur with pathophysiological deficits following sub-chronic phencyclidine administration in the rat. Behav Brain Res 194:230–235
Jenkins TA, Harte MK, Reynolds GP (2010) Effect of subchronic phencyclidine administration on sucrose preference and hippocampal parvalbumin immunoreactivity in the rat. Neurosci Lett 471:144–147
Jiao D, Liu Y, Li X, Liu J, Zhao M (2015) The role of the GABA system in amphetamine-type stimulant use disorders. Front Cell Neurosci 9:162
Keilhoff G, Becker A, Grecksch G, Wolf G, Bernstein HG (2004) Repeated application of ketamine to rats induces changes in the hippocampal expression of parvalbumin, neuronal nitric oxide synthase and cFOS similar to those found in human schizophrenia. Neuroscience 126:591–598
Kerdsan W, Thanoi S, Nudmamud-Thanoi S (2009) Changes in glutamate/NMDA receptor subunit 1 expression in rat brain after acute and subacute exposure to methamphetamine. J Biomed Biotechnol 2009:329631
Kerdsan W, Thanoi S, Nudmamud-Thanoi S (2012) Changes in the neuronal glutamate transporter EAAT3 in rat brain after exposure to methamphetamine. Basic Clin Pharmacol Toxicol 111:275–278
Kuczenski R, Everall IP, Crews L, Adame A, Grant I, Masliah E (2007) Escalating dose-multiple binge methamphetamine exposure results in degeneration of the neocortex and limbic system in the rat. Exp Neurol 207:42–51
Morshedi MM, Meredith GE (2007) Differential laminar effects of amphetamine on prefrontal parvalbumin interneurons. Neuroscience 149:617–624
Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates, 6th edn. Academic Press, Burlington
Reynolds GP, Abdul-Monim Z, Neill JC, Zhang ZJ (2004) Calcium binding protein markers of GABA deficits in schizophrenia—postmortem studies and animal models. Neurotox Res 6:57–61
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
Todtenkopf MS, Stellar JR, Williams EA, Zahm DS (2004) Differnetial distribution of parvalbumin immunoreactive neurons in the striatum of cocaine sensitized rats. Neuroscience 127:35–42
Volkow N, Li TK (2005) The neuroscience of addiction. Nat Neurosci 8:1429–1430
Zhang ZJ, Reynolds GP (2002) A selective decrease in the relative density of parvalbumin-immunoreactive neurons in the hippocampus in schizophrenia. Schizophr Res 55:1–10
Zhang X, Lee TH, Xiong X, Chen Q, Davidson C, Wetsel WC, Ellinwood EH (2006) Methamphetamine induces long-term changes in GABAA receptor α2 subunit and GAD67 expression. Biochem Biophys Res Commun 351:300–305
Zhu JP, Xu W, Angulo JA (2006) Methamphetamine-induced cell death: selective vulnerability in neuronal subpopulations of the striatum in mice. Neuroscience 140:607–622
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This study was supported by the Naresuan University Research Fund and a grant from the Thailand Research Fund through the Royal Golden Jubilee Ph.D. Program (PHD/0368/2551).
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All applicable international, national, and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.
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Veerasakul, S., Thanoi, S., Reynolds, G.P. et al. Effect of Methamphetamine Exposure on Expression of Calcium Binding Proteins in Rat Frontal Cortex and Hippocampus. Neurotox Res 30, 427–433 (2016). https://doi.org/10.1007/s12640-016-9628-2
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DOI: https://doi.org/10.1007/s12640-016-9628-2