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Naloxone Ameliorates Spatial Memory Deficits and Hyperthermia Induced by a Neurotoxic Methamphetamine Regimen in Male Rats

Solmaz Khalifeh, Mehdi Khodamoradi, Vahid Hajali, Hamed Ghazvini, Lelia Eliasy, Afshin Kheradmand, Vahid Farnia, Javad Akhtari, Kaveh Shahveisi, Hossein Ghalehnoei

Background: Methamphetamine (METH) as a synthetic psychostimulant is being increasingly recognized as a worldwide problem, which may induce memory impairment. On the other hand, it is well established that naloxone, an opiate antagonist, has some beneficial effects on learning and memory. The present research aimed at evaluating naloxone effects on spatial learning and memory impairment triggered by a neurotoxic regimen of METH in male rats. Materials and Methods: The animals received the subcutaneous (sc) regimen of METH (4×6 mg/kg at 2-h intervals), intraperitoneal (ip) naloxone (4×1 mg/kg at 2-h intervals), or normal saline at four events. The Nal-METH group of rats received four naloxone injections (1 mg/kg, ip) 30 min before each METH injection (6 mg/kg, sc) at 2-h intervals. Seven days later, they were evaluated for spatial learning and memory in the Morris Water Maze (MWM) task. Result: METH regimen induced hyperthermia, as well as a poor performance, in the acquisition and retention phases of the task, indicating spatial learning and memory impairment compared to the controls. Naloxone administration (1 mg/kg, ip) before each METH injection led to significant attenuations of both hyperthermia and METH adverse effects on the rat performance in the MWM task. Conclusion: The results revealed that pretreatment with the opiate antagonist naloxone could prevent METH adverse effects on body temperature and memory performance. It seems that the opioidergic system and hyperthermia may, at least partially, be involved in METH effects on spatial memory. [GMJ. 2019;8:e1182]

Methamphetamine Hydrochloride; Naloxone Hydrochloride; Spatial Memories; Hyperthermia

Hanson GR, Rau KS, Fleckenstein AE. The methamphetamine experience: a NIDA partnership. Neuropharmacology. 2004;47:92-100.

https://doi.org/10.1016/j.neuropharm.2004.06.004

PMid:15464128

Farrell M, Marsden J, Ali R, Ling W. Methamphetamine: drug use and psychoses becomes a major public health issue in the Asia Pacific region. Addiction. 2002;97(7):771-2.

https://doi.org/10.1046/j.1360-0443.2002.00195.x

PMid:12133111

Gibson DR, Leamon MH, Flynn N. Epidemiology and public health consequences of methamphetamine use in California's Central Valley. J Psychoactive Drugs. 2002;34(3):313-9.

https://doi.org/10.1080/02791072.2002.10399969

PMid:12422943

Sommers I, Baskin D, Baskin-Sommers A. Methamphetamine use among young adults: health and social consequences. Addict Behav. 2006;31(8):1469-76.

https://doi.org/10.1016/j.addbeh.2005.10.004

PMid:16309848

Ghazvini H, Shabani M, Asadi-Shekaari M, Khalifeh S, Esmaeilpour K, Khodamoradi M, et al. Estrogen and progesterone replacement therapy prevent methamphetamine-induced synaptic plasticity impairment in ovariectomized rats. Addiction & health. 2016;8(3):145.

PMid:28496953 PMCid:PMC5422011

Nagai T, Takuma K, Dohniwa M, Ibi D, Mizoguchi H, Kamei H, et al. Repeated methamphetamine treatment impairs spatial working memory in rats: reversal by clozapine but not haloperidol. Psychopharmacology (Berl). 2007;194(1):21-32.

https://doi.org/10.1007/s00213-007-0820-1

PMid:17514479

Simon SL, Domier C, Carnell J, Brethen P, Rawson R, Ling W. Cognitive impairment in individuals currently using methamphetamine. Am J Addict. 2000;9(3):222-31.

https://doi.org/10.1080/10550490050148053

PMid:11000918

Dean AC, Groman SM, Morales AM, London ED. An evaluation of the evidence that methamphetamine abuse causes cognitive decline in humans. Neuropsychopharmacology. 2013;38(2):259-74.

https://doi.org/10.1038/npp.2012.179

PMid:22948978 PMCid:PMC3527116

Ghazvini H, Khaksari M, Esmaeilpour K, Shabani M, Asadi-Shekaari M, Khodamoradi M, et al. Effects of treatment with estrogen and progesterone on the methamphetamine-induced cognitive impairment in ovariectomized rats. Neurosci Lett. 2016;619:60-7.

https://doi.org/10.1016/j.neulet.2016.02.057

PMid:26944454

Matsumoto RR, Seminerio MJ, Turner RC, Robson MJ, Nguyen L, Miller DB, et al. Methamphetamine-induced toxicity: an updated review on issues related to hyperthermia. Pharmacol Ther. 2014 Oct;144(1):28-40.

https://doi.org/10.1016/j.pharmthera.2014.05.001

PMid:24836729 PMCid:PMC4700537

Racinais S, Gaoua N, Grantham J. Hyperthermia impairs short-term memory and peripheral motor drive transmission. J Physiol. 2008 Oct 1;586(19):4751-62.

https://doi.org/10.1113/jphysiol.2008.157420

PMid:18703579 PMCid:PMC2607529

Schad CA, Justice JB, Holtzman SG. Naloxone reduces the neurochemical and behavioral effects of amphetamine but not those of cocaine. Eur J Pharmacol. 1995;275(1):9-16.

https://doi.org/10.1016/0014-2999(94)00726-N

Ghazvini H, Rezayof A, Ghasemzadeh Z, Zarrindast M-R. μ-Opioid and N-methyl-D-aspartate receptors in the amygdala contribute to minocycline-induced potentiation of morphine analgesia in rats. Behav Pharmacol. 2015;26(4):383-92.

https://doi.org/10.1097/FBP.0000000000000126

PMid:25563202

Funahashi M, Kohda H, Hori O, Hayashida H, Kimura H. Potentiating effect of morphine upon d-methamphetamine-induced hyperthermia in mice. Effects of naloxone and haloperidol. Pharmacol Biochem Behav. 1990;36(2):345-50.

https://doi.org/10.1016/0091-3057(90)90415-E

Canli T, Cook RG, Miczek KA. Opiate antagonists enhance the working memory of rats in the radial maze. Pharmacol Biochem Behav. 1990;36(3):521-5.

https://doi.org/10.1016/0091-3057(90)90250-L

Derrick BE, Weinberger SB, Martinez JL. Opioid receptors are involved in an NMDA receptor-independent mechanism of LTP induction at hippocampal mossy fiber-CA3 synapses. Brain Res Bull. 1991;27(2):219-23.

https://doi.org/10.1016/0361-9230(91)90071-Q

Beatty WW. Opiate antagonists, morphine and spatial memory in rats. Pharmacol Biochem Behav. 1983;19(3):397-401.

https://doi.org/10.1016/0091-3057(83)90108-9

Galea LA, Saksida L, Kavaliers M, Ossenkopp K-P. Naloxone facilitates spatial learning in a water-maze task in female, but not male, adult nonbreeding meadow voles. Pharmacol Biochem Behav. 1994;47(2):265-71.

https://doi.org/10.1016/0091-3057(94)90009-4

Omrani A, Ghadami M, Fathi N, Tahmasian M, Fathollahi Y, Touhidi A. Naloxone improves impairment of spatial performance induced by pentylenetetrazol kindling in rats. Neuroscience. 2007;145(3):824-31.

https://doi.org/10.1016/j.neuroscience.2006.12.049

PMid:17289274

Balsara JJ, Nandal NV, Burte NP, Jadhav JH, Chandorkar AG. Effects of naloxone on methamphetamine and apomorphine stereotypy and on haloperidol catalepsy in rats. Psychopharmacology (Berl). 1984;82(3):237-40.

https://doi.org/10.1007/BF00427781

Camarasa J, Rodrigo T, Pubill D, Escubedo E. Memantine is a useful drug to prevent the spatial and non-spatial memory deficits induced by methamphetamine in rats. Pharmacol Res. 2010;62(5):450-6.

https://doi.org/10.1016/j.phrs.2010.05.004

PMid:20553881

Hajali V, Sheibani V, Ghazvini H, Ghadiri T, Valizadeh T, Saadati H, et al. Effect of castration on the susceptibility of male rats to the sleep deprivation-induced impairment of behavioral and synaptic plasticity. Neurobiol Learn Mem. 2015;123:140-8.

https://doi.org/10.1016/j.nlm.2015.05.008

PMid:26079215

Khodamoradi M, Asadi-Shekaari M, Esmaeili-Mahani S, Esmaeilpour K, Sheibani V. Effects of genistein on cognitive dysfunction and hippocampal synaptic plasticity impairment in an ovariectomized rat kainic acid model of seizure. Eur J Pharmacol. 2016;786:1-9.

https://doi.org/10.1016/j.ejphar.2016.05.028

PMid:27235295

Herring NR, Schaefer TL, Gudelsky GA, Vorhees CV, Williams MT. Effect of (+)-methamphetamine on path integration learning, novel object recognition, and neurotoxicity in rats. Psychopharmacology (Berl). 2008;199(4):637-50.

https://doi.org/10.1007/s00213-008-1183-y

PMid:18509623 PMCid:PMC2562284

North A, Swant J, Salvatore MF, Gamble-George J, Prins P, Butler B, et al. Chronic methamphetamine exposure produces a delayed, long-lasting memory deficit. Synapse. 2013;67(5):245-57.

https://doi.org/10.1002/syn.21635

PMid:23280858 PMCid:PMC3831527

Belcher AM, O'Dell SJ, Marshall JF. Impaired object recognition memory following methamphetamine, but not p-chloroamphetamine-or d-amphetamine-induced neurotoxicity. Neuropsychopharmacology. 2005;30(11):2026-34.

https://doi.org/10.1038/sj.npp.1300771

PMid:15900317

Schröder N, O'Dell SJ, Marshall JF. Neurotoxic methamphetamine regimen severely impairs recognition memory in rats. Synapse. 2003;49(2):89-96.

https://doi.org/10.1002/syn.10210

PMid:12740864

Bliss TV, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993;361(6407):31-9.

https://doi.org/10.1038/361031a0

PMid:8421494

Albers DS, Sonsalla PK. Methamphetamine-induced hyperthermia and dopaminergic neurotoxicity in mice: pharmacological profile of protective and nonprotective agents. J Pharmacol Exp Ther. 1995 Dec;275(3):1104-14.

PMid:8531070

Izquierdo I. Effect of β-endorphin and naloxone on acquisition, memory, and retrieval of shuttle avoidance and habituation learning in rats. Psychopharmacology (Berl). 1980;69(1):111-5.

https://doi.org/10.1007/BF00426531

Messing RB, Jensen RA, Martinez JL, Spiehler VR, Vasquez BJ, Soumireu-Mourat B, et al. Naloxone enhancement of memory. Behav Neural Biol. 1979;27(3):266-75.

https://doi.org/10.1016/S0163-1047(79)92328-8

Decker MW, Introini-Collison IB, McGaugh JL. Effects of naloxone on Morris water maze learning in the rat: Enhanced acquisition with pretraining but not posttraining administration. Psychobiology. 1989;17(3):270-5.

https://doi.org/10.1007/BF03337778

McNamara RK, Skelton RW. Pretraining morphine impairs acquisition and performance in the Morris water maze: Motivation reduction rather than anmesia. Psychobiology. 1991;19(4):313-22.

Thornhill J, Hirst M, Gowdey C. Changes in the hyperthermic responses of rats to daily injections of morphine and the antagonism of the acute response by naloxone. Can J Physiol Pharmacol. 1978;56(3):483-9.

https://doi.org/10.1139/y78-072

PMid:667723

Ushijima I, Tanaka M, Tsuda A, Koga S, Nagasaki N. Differential effects of morphine on core temperature in stressed and non-stressed rats. Eur J Pharmacol. 1985;112(3):331-7.

https://doi.org/10.1016/0014-2999(85)90778-2

Lal H, Miksic S, Smith N. Naloxone antagonism of conditioned hyperthermia: an evidence for release of endogenous opioid. Life Sci. 1976 May 1;18(9):971-5.

https://doi.org/10.1016/0024-3205(76)90417-3

Zhao H, Xu H, Xu X. Effects of naloxone on the long-term potentiation of EPSPs from the pathway of Schaffer collateral to CA1 region of hippocampus in aged rats with declined memory. Brain Res. 2004;996(1):111-6.

https://doi.org/10.1016/j.brainres.2003.10.017

PMid:14670637

Wagner JJ, Terman GW, Chavkin C. Endogenous dynorphins inhibit excitatory neurotransmission and block LTP induction in the hippocampus. Nature. 1993;363(6428):451-4.

https://doi.org/10.1038/363451a0

PMid:8099201 PMCid:PMC2096733

Weisskopf MG, Zalutsky RA, Nicoll RA. The opioid peptide dynorphin mediates heterosynaptic depression of hippocampal mossy fibre synapses and modulates long-term potentiation. Nature. 1993;362(6419):423-7.

https://doi.org/10.1038/362423a0

PMid:8096624

Chang RC, Rota C, Glover RE, Mason RP, Hong J-S. A novel effect of an opioid receptor antagonist, naloxone, on the production of reactive oxygen species by microglia: a study by electron paramagnetic resonance spectroscopy. Brain Res. 2000;854(1):224-9.

https://doi.org/10.1016/S0006-8993(99)02267-2

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