The effect of medial prefrontal cortex electrical stimulation on passive avoidance memory in healthy and addict rats


1 Department of Physiology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Basic Sciences, Isfahan Payame Noor University, Isfahan, Iran


Background: The medial prefrontal cortex (mPFC) is a part of brain reward system involved in cognitive functions such as learning and memory. The mPFC receives strong dopaminergic innervations from ventral tegmental area (VTA) that comprises a portion of the mesolimbic dopaminergic system (MLDS), and sends glutamatergic projections to both the VTA and nucleus accumbens (NAc).
Materials and Methods: In this study, male Wister rats weighing 250-350 g were used. The effect of medial prefrontal cortex (mPFC) electrical stimulation with different current intensities (25, 50,100, and 150 µA) in healthy and addicted rats on passive avoidance memory was studied here.
Results: This study showed that 25 and 150 µA had no effect on improving avoidance memory in rats. Current intensities of 50 and 100 µA differ significantly with 25 and 150 µA. The PL of mPFC contributes to memory processing.
Conclusions: The electrical stimulations of prelimbic with 50 and 100 µA current intensities were improved avoidance memory in addicted rats while learning impairment is caused in healthy rats while the electrical stimulation with these used current intensities.


Vertes RP. Interactions among the medial prefrontal cortex, hippocampus and midline thalamus in emotional and cognitive processing in the rat. Neuroscience 2006;142:1-20.  Back to cited text no. 1
Heidbreder CA, Groenewegen HJ. The medial prefrontal cortex in the rat: Evidence for a dorso-ventral distinction based upon functional and anatomical characteristics. Neuro Sci Bio Behav Rev 2003;27:555-79.  Back to cited text no. 2
Taber MT, Fibiger HC. Electrical stimulation of the prefrontal cortex increases dopamine release in the nucleus accumbens of the rat: Modulation by metabotropic glutamate receptors. J Neurosci 1995;15:3896-904.  Back to cited text no. 3
Tzschentke TM. The medial prefrontal cortex as a part of the brain reward system. Amino Acids 2000;19:211-9.  Back to cited text no. 4
Hao Y, Yang JY, Guo M, Wu CF, Wu MF. Morphine decreases extracellular levels of glutamate in the anterior cingulated cortex: An in vivo microdialysis study in freely moving rats. Brain Res 2005;1040:191-6.  Back to cited text no. 5
Liang J, Ping XJ, Li YJ, Ma YY, Wu LZ, Han JS, et al. Morphine-induced conditioned place preference in rats is inhibited by electro acupuncture at 2 Hz: Role of encephalin in the nucleus accumbens. Neuropharmacology 2010;58:233-40.  Back to cited text no. 6
Tzschentke TM, Schmidt WJ. Functional relationship among medial prefrontal cortex, nucleus accumbens, and ventral tegmental area in locomotion and reward. Crit Rev Neurobiol 2000;14:131-42.  Back to cited text no. 7
Paxinos G, Watson C. The rat brain in stereotaxic coordinates. New York: Academic Press; 2002.  Back to cited text no. 8
Juckel G, Mendlin A, Jacobs BL. Electrical stimulation of rat medial prefrontal cortex enhances forebrain serotonin output: Implications for electroconvulsive therapy and transcranial magnetic stimulation in depression. Neuropsychopharmacology 1999;21:391-8.  Back to cited text no. 9
Koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsychopharmacology 2009;35:217-38.  Back to cited text no. 10
Koob GF. Drugs of abuse: Anatomy, pharmacology and function of reward pathways. Trends Pharmacol Sci 1992;13:177-84.  Back to cited text no. 11
Tzschentke TM. Pharmacology and behavioral pharmacology of the mesocortical dopamine system. Prog Neurobiol 2001;63:241-320.  Back to cited text no. 12
Hao Y, Yang J, Sun J, Qi J, Dong Y, Wu CF. Lesions of the medial prefrontal cortex prevent the acquisition but not reinstatement of morphine-induced conditioned place preference in mice. Neurosci Lett 2008;433:48-53.  Back to cited text no. 13
You ZB, Tzschentke TM, Brodin E, Wise RA. Electrical stimulation of the prefrontal cortex increases cholecystokinin, glutamate, and dopamine release in the nucleus accumbens: An in vivo micro dialysis study in freely moving rats. J Neurosci 1998;18:6492-500.  Back to cited text no. 14
Margolis EB, Lock H, Chefer VI, Shippenberg TS, Hjelmstad GO, Fields HL. Opioids selectively control dopaminergic neurons projecting to the prefrontal cortex. Proc Natl Acad Sci U SA 2006;103:2938-42.  Back to cited text no. 15
Kalivas PW, LaLumiere RT, Knackstedt L, Shen H. Glutamate transmission in addiction. Neuropharmacology 2009;56:169-73.  Back to cited text no. 16
Koob GF, Sanna PP, Bloom FE. Neuroscience of addiction. Neuron 1998;21:467-76.  Back to cited text no. 17
Rajaei Z, Alaei H, Nasimi A, Amini H, Ahmadiani A. Ascorbate reduces morphine-induced extracellular DOPAC level in the nucleus accumbens: A micro dialysis study in rats. Brain Res 2005;1053:62-6.  Back to cited text no. 18
Tzschentke TM, Schmidt WJ. Glutamatergic mechanisms in addiction. Molecular Psychiatry 2003;8:373-82.  Back to cited text no. 19
Cowan A, Lewis JW, Macfarlane IR. Agonist and antagonist properties of buprenorphine, a new antinociceptive agent. Br J Pharmacol 1977;60:537-45.  Back to cited text no. 20
Gros C, Giros B, Schwartz JC. Identification of aminopeptidase M as an enkephalin-inactivating enzyme in rat cerebral membranes. Biochemistry 1985;24:2179-85.  Back to cited text no. 21