Blockade of Glutamate Receptors within the Prelimbic Cortex Attenuate Concentration of Excitatory Amino Acids in the Morphine Self-administration in Rats

Document Type : Original Article

Authors

1 Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran

2 Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: The attitude of research on addiction has been done on the key role of glutamate. As a regard, the prelimbic cortex (PrL) has an important role in addiction, learning, and memory. We tried to investigate the level of glutamate and aspartate concentration after glutamate receptors blockade in this region in the morphine-addicted rats. Materials and Methods: In this study, we examined the effects of local infusion of the N-methyl-D-aspartate receptor and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonists, 2-amino-5-phosphonovaleric acid (AP5), and 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX), into the PrL cortex on the level of excitatory amino acids (EAAs) and glycine. After 11 days of self-administration, the prelimbic area of the brain was taken out, and the EAAs and glycine concentration was measured by high-performance liquid chromatography. Results: Morphine resulted in the significant increase in the EAAs concentration within this area (P ≤ 0.001). Microinjection of AP5 into this region before using of morphine significantly decreased the morphine-induced glutamate and aspartate concentration (P ≤ 0.001). CNQX had the same effect and significantly reduced the EAAs concentration compared to the morphine group (P ≤ 0.001). In addition, microinjection of AP5 and CNQX simultaneously increased glycine concentration (P ≤ 0.001). Conclusions: These results show that morphine stimulates the EAAs release in the prelimbic area. It seems that microinjection of AP5 or CNQX in this region is effective in reducing morphine-induced EAA. It is suggested that EAA transmission in the PrL cortex may be a possible target for treatment of morphine addiction.

Keywords

1.
Miller CA, Marshall JF. Altered prelimbic cortex output during cue-elicited drug seeking. J Neurosci 2004;24:6889-97.  Back to cited text no. 1
    
2.
Ventura R, Alcaro A, Puglisi-Allegra S. Prefrontal cortical norepinephrine release is critical for morphine-induced reward, reinstatement and dopamine release in the nucleus accumbens. Cereb Cortex 2005;15:1877-86.  Back to cited text no. 2
    
3.
Ruzicka BB, Jhamandas KH. Excitatory amino acid action on the release of brain neurotransmitters and neuromodulators: Biochemical studies. Prog Neurobiol 1993;40:223-47.  Back to cited text no. 3
    
4.
Gass JT, Olive MF. Glutamatergic substrates of drug addiction and alcoholism. Biochem Pharmacol 2008;75:218-65.  Back to cited text no. 4
    
5.
Tomek SE, Lacrosse AL, Nemirovsky NE, Olive MF. NMDA receptor modulators in the treatment of drug addiction. Pharmaceuticals (Basel) 2013;6:251-68.  Back to cited text no. 5
    
6.
Guo Y, Wang HL, Xiang XH, Zhao Y. The role of glutamate and its receptors in mesocorticolimbic dopaminergic regions in opioid addiction. Neurosci Biobehav Rev 2009;33:864-73.  Back to cited text no. 6
    
7.
Carr DB, Sesack SR. Projections from the rat prefrontal cortex to the ventral tegmental area: Target specificity in the synaptic associations with mesoaccumbens and mesocortical neurons. J Neurosci 2000;20:3864-73.  Back to cited text no. 7
    
8.
Lorrain DS, Baccei CS, Bristow LJ, Anderson JJ, Varney MA. Effects of ketamine and N-methyl-D-aspartate on glutamate and dopamine release in the rat prefrontal cortex: Modulation by a group II selective metabotropic glutamate receptor agonist LY379268. Neuroscience 2003;117:697-706.  Back to cited text no. 8
    
9.
Adams BW, Moghaddam B. Effect of clozapine, haloperidol, or M100907 on phencyclidine-activated glutamate efflux in the prefrontal cortex. Biol Psychiatry 2001;50:750-7.  Back to cited text no. 9
    
10.
Steciuk M, Kram M, Kramer GL, Petty F. Immobilization-induced glutamate efflux in medial prefrontal cortex: Blockade by (+)-mk-801, a selective NMDA receptor antagonist. Stress 2000;3:195-9.  Back to cited text no. 10
    
11.
Nowak K, Meyza K, Nikolaev E, Hunt MJ, Kasicki S. Local blockade of NMDA receptors in the rat prefrontal cortex increases c-Fos expression in multiple subcortical regions. Acta Neurobiol Exp (Wars) 2012;72:207-18.  Back to cited text no. 11
    
12.
Alaei H, Huotari M, Piepponen PT, Ahtee L, Hanninen O, Mannisto PT. Morphine releases glutamate through AMPA receptors in the ventral tegmental area: A microdialysis study in conscious rats. Med J I R Iran 2003;17:225-31.  Back to cited text no. 12
    
13.
Paxinos G, Watson C. The rat Brain in Stereotaxic Coordinates. 5th ed. San Diego, CA: Academic Press; 2005.  Back to cited text no. 13
    
14.
De Jaeger X, Bishop SF, Ahmad T, Lyons D, Ng GA, Laviolette SR, et al. The effects of AMPA receptor blockade in the prelimbic cortex on systemic and ventral tegmental area opiate reward sensitivity. Psychopharmacology (Berl) 2013;225:687-95.  Back to cited text no. 14
    
15.
Bishop SF, Lauzon NM, Bechard M, Gholizadeh S, Laviolette SR. NMDA receptor hypofunction in the prelimbic cortex increases sensitivity to the rewarding properties of opiates via dopaminergic and amygdalar substrates. Cereb Cortex 2011;21:68-80.  Back to cited text no. 15
    
16.
Sahraei H, Poorheidari G, Foadaddini M, Khoshbaten A, Asgari A, Noroozzadeh A, et al. Effects of nitric oxide on morphine self-administration in rat. Pharmacol Biochem Behav 2004;77:111-6.  Back to cited text no. 16
    
17.
Alaei H, Pourshanazari AA, Rafati A. Electrical stimulation of nucleus raphe dorsalis changes morphine self-administration and withdrawal symptoms in rats. Pathophysiology 2002;9:1.  Back to cited text no. 17
    
18.
Clarke G, O'Mahony S, Malone G, Dinan TG. An isocratic high performance liquid chromatography method for the determination of GABA and glutamate in discrete regions of the rodent brain. J Neurosci Methods 2007;160:223-30.  Back to cited text no. 18
    
19.
Knox D, Perrine SA, George SA, Galloway MP, Liberzon I. Single prolonged stress decreases glutamate, glutamine, and creatine concentrations in the rat medial prefrontal cortex. Neurosci Lett 2010;480:16-20.  Back to cited text no. 19
    
20.
Piepponen TP, Skujins A. Rapid and sensitive step gradient assays of glutamate, glycine, taurine and gamma-aminobutyric acid by high-performance liquid chromatography-fluorescence detection with o-phthalaldehyde-mercaptoethanol derivatization with an emphasis on microdialysis samples. J Chromatogr B Biomed Sci Appl 2001;757:277-83.  Back to cited text no. 20
    
21.
Farahmandfar M, Karimian SM, Zarrindast MR, Kadivar M, Afrouzi H, Naghdi N, et al. Morphine sensitization increases the extracellular level of glutamate in CA1 of rat hippocampus via μ-opioid receptor. Neurosci Lett 2011;494:130-4.  Back to cited text no. 21
    
22.
Zheng P, Yang L, Chen M. Morphine Selectively Promotes Glutamate Release from Glutamatergic Terminals of Projection Neurons from Medial Prefrontal Cortex to Dopamine Neurons of Ventral Tegmental Area. BioRxiv Preprint First Posted Online; 2017. Available from: http://www.dx.doi.org/10.1101/133090.  Back to cited text no. 22
    
23.
Ceglia I, Carli M, Baviera M, Renoldi G, Calcagno E, Invernizzi RW, et al. The 5-HT receptor antagonist M100,907 prevents extracellular glutamate rising in response to NMDA receptor blockade in the mPFC. J Neurochem 2004;91:189-99.  Back to cited text no. 23
    
24.
LaLumiere RT, Kalivas PW. Glutamate release in the nucleus accumbens core is necessary for heroin seeking. J Neurosci 2008;28:3170-7.  Back to cited text no. 24
    
25.
McFarland K, Lapish CC, Kalivas PW. Prefrontal glutamate release into the core of the nucleus accumbens mediates cocaine-induced reinstatement of drug-seeking behavior. J Neurosci 2003;23:3531-7.  Back to cited text no. 25
    
26.
Xie X, Steketee JD. Repeated exposure to cocaine alters the modulation of mesocorticolimbic glutamate transmission by medial prefrontal cortex group II metabotropic glutamate receptors. J Neurochem 2008;107:186-96.  Back to cited text no. 26
    
27.
De Vries TJ, Shippenberg TS. Neural systems underlying opiate addiction. J Neurosci 2002;22:3321-5.  Back to cited text no. 27
    
28.
D'Souza MS. Glutamatergic transmission in drug reward: Implications for drug addiction. Front Neurosci 2015;9:404.  Back to cited text no. 28
    
29.
Del Arco A, Mora F. NMDA and AMPA/kainate glutamatergic agonists increase the extracellular concentrations of GABA in the prefrontal cortex of the freely moving rat: Modulation by endogenous dopamine. Brain Res Bull 2002;57:623-30.  Back to cited text no. 29
    
30.
Cavallero A, Marte A, Fedele E. L-aspartate as an amino acid neurotransmitter: Mechanisms of the depolarization-induced release from cerebrocortical synaptosomes. J Neurochem 2009;110:924-34.  Back to cited text no. 30
    
31.
Liu Y, Huang D, Wen R, Chen X, Yi H. Glycine receptor-mediated inhibition of medial prefrontal cortical pyramidal cells. Biochem Biophys Res Commun 2015;456:666-9.  Back to cited text no. 31
    
32.
Chau P, Süderpalm B, Ericson M. The mGluR5 antagonist MPEP elevates accumbal dopamine and glycine levels; interaction with strychnine-sensitive glycine receptors. Addict Biol 2011;16:591-9.  Back to cited text no. 32
    
33.
Shin KW, Hong JT, Yoo HS, Song S, Oh KW. Inhibitory effects of glycine on morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity in mice. Arch Pharm Res 2003;26:1074-8.  Back to cited text no. 33