Extremely low-frequency electromagnetic field exposure during chronic morphine treatment strengthens downregulation of dopamine D2 receptors in rat dorsal hippocampus after morphine withdrawal

The aim of this study was to investigate the effect of extremely low-frequency electromagnetic field (ELF-EMF) exposure during morphine treatment on dopamine D2 receptor (D2R) density in the rat dorsal hippocampus following withdrawal. Rats were exposed to ELF-EMF (20 Hz, 14 mT) or sham exposed for 1h per day before injection of morphine (10mg/kg, i.p.) once daily for 12 days. The saline control group was sham exposed for the same period. Immunohistochemistry was used to detect the density of D2Rs on the 1st, 3rd and 5th morphine withdrawal days. The results showed that the density of D2Rs in sham-exposed morphine-treated rats on the 1st and 3rd days of morphine withdrawal was significantly lower than that of the saline control group. The ELF-EMF-exposed morphine group also exhibited a significantly lower density of D2Rs on the 1st and 3rd withdrawal days relative to the sham-exposed morphine group. However, the D2R density in both groups tended to recover as morphine withdrawal days increased. The results suggest that dorsal hippocampal D2Rs are sensitive to morphine withdrawal and that this is potentiated by ELF-EMF pre-exposure during morphine treatment.

[1]  Mark G. Packard,et al.  The dopaminergic mesencephalic projections to the hippocampal formation in the rat , 1997, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[2]  P Cerretelli,et al.  Biological effects of prolonged exposure to ELF electromagnetic fields in rats: III. 50 Hz electromagnetic fields. , 1998, Bioelectromagnetics.

[3]  Rita Z. Goldstein,et al.  Role of Dopamine, the Frontal Cortex and Memory Circuits in Drug Addiction: Insight from Imaging Studies , 2002, Neurobiology of Learning and Memory.

[4]  T. Shippenberg,et al.  Neural Systems Underlying Opiate Addiction , 2002, The Journal of Neuroscience.

[5]  Influence of 50 Hz Frequency Sinusoidal Magnetic Field on the Blood‐Brain Barrier Permeability of Diabetic Rats , 2004, Bioelectromagnetics.

[6]  Yan Chen,et al.  Curcumin, a potent anti-tumor reagent, is a novel histone deacetylase inhibitor regulating B-NHL cell line Raji proliferation , 2005, Acta Pharmacologica Sinica.

[7]  G. Koob.  Drugs of abuse: anatomy, pharmacology and function of reward pathways. , 1992, Trends in pharmacological sciences.

[8]  F. Weiss,et al.  The dopamine hypothesis of reward: past and current status , 1999, Trends in Neurosciences.

[9]  W. Corrigall,et al.  Conditioned place preference produced by intra-hippocampal morphine , 1988, Pharmacology Biochemistry and Behavior.

[10]  Veeranna,et al.  Evidence for the behavioral supersensitivity of dopamine D2 receptors without receptor up-regulation in morphine-abstinent rats , 1993, Brain Research.

[11]  M. Cebeira,et al.  Modifications of striatal D2 dopaminergic postsynaptic sensitivity during development of morphine tolerance-dependence in mice , 1992, Pharmacology Biochemistry and Behavior.

[12]  Y. Li,et al.  Dynamic changes in orbitofrontal neuronal activity in rats during opiate administration and withdrawal , 2006, Neuroscience.

[13]  T. Robbins,et al.  Neural systems of reinforcement for drug addiction: from actions to habits to compulsion , 2005, Nature Neuroscience.

[14]  E. Nestler.  Is there a common molecular pathway for addiction? , 2005, Nature Neuroscience.

[15]  A. Sieroń,et al.  Alternating extremely low frequency magnetic field increases turnover of dopamine and serotonin in rat frontal cortex , 2004, Bioelectromagnetics.

[16]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[17]  R. Spanagel,et al.  Endogenous κ-opioid systems in opiate withdrawal: role in aversion and accompanying changes in mesolimbic dopamine release , 1994, Psychopharmacology.

[18]  R Brus,et al.  Influence of alternating low frequency magnetic fields on reactivity of central dopamine receptors in neonatal 6‐hydroxydopamine treated rats , 2001, Bioelectromagnetics.

[19]  Yuanye Ma,et al.  Effects of extremely low-frequency electromagnetic fields on morphine-induced conditioned place preferences in rats , 2005, Neuroscience Letters.

[20]  M. Pistis,et al.  Lasting reduction in mesolimbic dopamine neuronal activity after morphine withdrawal , 1999, The European journal of neuroscience.

[21]  M. Soliman,et al.  Alteration of D1 and D2 dopaminergic receptor kinetics in specific rat brain regions following repeated administration of opiates. , 1995, Pharmacology.

[22]  R. Quirion,et al.  Local modulation of hippocampal acetylcholine release by dopamine D1 receptors: a combined receptor autoradiography and in vivo dialysis study , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  G. Di Chiara,et al.  Neurobiology of opiate abuse. , 1992, Trends in pharmacological sciences.

[24]  G. Aston-Jones,et al.  Behavioral activation induced by D(2)-like receptor stimulation during opiate withdrawal. , 2000, The Journal of pharmacology and experimental therapeutics.

[25]  R. J. McDonald,et al.  Dorsal/ventral hippocampus, fornix, and conditioned place preference , 2001, Hippocampus.

[26]  E. Nestler.  Total Recall--the Memory of Addiction , 2001, Science.

[27]  S. R. Vorel,et al.  Relapse to Cocaine-Seeking After Hippocampal Theta Burst Stimulation , 2001, Science.

[28]  T. Robinson,et al.  Withdrawal from morphine or amphetamine: different effects on dopamine in the ventral-medial striatum studied with microdialysis , 1994, Brain Research.

[29]  J. Meador-Woodruff.  Update on dopamine receptors. , 1994, Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists.

[30]  H. Sahraei,et al.  Involvement of Dopamine Receptors of the Dorsal Hippocampus on the Acquisition and Expression of Morphine-Induced Place Preference in Rats , 2003, Journal of psychopharmacology.

[31]  R. Hesketh,et al.  Biological responses to electromagnetic fields 1 , 1998, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[32]  G. Aston-Jones,et al.  Involvement of D2 dopamine receptors in the nucleus accumbens in the opiate withdrawal syndrome , 1994, Nature.

[33]  F. Georges,et al.  Chronic morphine exposure and spontaneous withdrawal are associated with modifications of dopamine receptor and neuropeptide gene expression in the rat striatum , 1999, The European journal of neuroscience.

[34]  Yan Yang,et al.  The dynamics of hippocampal sensory gating during the development of morphine dependence and withdrawal in rats , 2005, Neuroscience Letters.