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Electrical stimulation mPFC affects morphine addiction by changing glutamate concentration in the ventral tegmental area

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Abstract

Morphine addiction is known as a serious social problem. Medial prefrontal cortex (mPFC) and ventral tegmental area (VTA) are two important sites of the brain that contribute to this type of addiction, and a complicated relation exists in between. In addition, neurotransmitters like glutamate and γ--Amino Butyric Acid (GABA) play an important role in the formation of these relations. Thus, the present study was undertaken to investigate these relations by evaluating the level of associated changes in the indicated neurotransmitters in the VTA, using HPLC method. This was performed after electrical stimulation and inducing lesion of mPFC and through microinjections of N-Methyl-D-Aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists, respectively AP5 and CNQX, into the VTA of addicted rats. Our results showed that intra-peritoneal (i.p.) administration of morphine in 9 days in the morphine group, and also electrical stimulation (100 μA) of mPFC, receiving (i.p.) morphine, caused an increase in the glutamate release in the VTA, compared to the control group, but the increase of glutamate levels in the VTA in the morphine-stimulation group was not significant, compared to the morphine group. Moreover, GABA release into this area was decreasing in morphine and morphine- stimulation groups, compared to the control group. Our findings also showed that electrical lesion (0.4 mA) of mPFC, and also microinjection of glutamate antagonists into the VTA, receiving (i.p.) morphine in rats, caused a decrease of glutamate in the VTA. Therefore, it could be concluded that the relation between mPFC and VTA is highly effective in the formation of reward system.

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Abbreviations

mPFC:

Medial prefrontal cortex

VTA:

ventral tegmental area

NMDA:

N-Methyl-D-Aspartate

AMPA:

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

GABA:

γ--Amino Butyric Acid

BNST:

stria terminalis

i.p:

Intraperitoneally

PL:

prelimbic

AP:

anterioposterior

ML:

mediolateral

DV:

dorsoventral

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Acknowledgments

The authors would like to express their gratitude to Isfahan University of Medical Sciences, Isfahan, Iran, without whose support.

Funding

This work was supported by Isfahan University of Medical Sciences.

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Authors and Affiliations

  1. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

    Asal Keramatian & Akram Eidi

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

    Hojjatallah Alaei & Maryam Radahmadi

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  1. Asal Keramatian
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  2. Hojjatallah Alaei
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  3. Akram Eidi
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  4. Maryam Radahmadi
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Correspondence to Hojjatallah Alaei.

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Keramatian, A., Alaei, H., Eidi, A. et al. Electrical stimulation mPFC affects morphine addiction by changing glutamate concentration in the ventral tegmental area. Metab Brain Dis 34, 1171–1180 (2019). https://doi.org/10.1007/s11011-019-00426-z

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