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Synapse. 2016 Aug;70(8):325-35. doi: 10.1002/syn.21905. Epub 2016 Apr 15.

Methamphetamine-induced enhancement of hippocampal long-term potentiation is modulated by NMDA and GABA receptors in the shell-accumbens.

Author information

1
Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
2
Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran.
3
Department of Physiology, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
4
Neurophysiology Research Center, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
5
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
6
Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
7
Department of Neuroscience, University of Florida, Gainesville, Florida, 323611.

Abstract

Addictive drugs modulate synaptic transmission in the meso-corticolimbic system by hijacking normal adaptive forms of experience-dependent synaptic plasticity. Psychostimulants such as METH have been shown to affect hippocampal synaptic plasticity, albeit with a less understood synaptic mechanism. METH is one of the most addictive drugs that elicit long-term alterations in the synaptic plasticity in brain areas involved in reinforcement learning and reward processing. Dopamine transporter (DAT) is one of the main targets of METH. As a substrate for DAT, METH decreases dopamine uptake and increases dopamine efflux via the transporter in the target brain regions such as nucleus accumbens (NAc) and hippocampus. Due to cross talk between NAc and hippocampus, stimulation of NAc has been shown to alter hippocampal plasticity. In this study, we tested the hypothesis that manipulation of glutamatergic and GABA-ergic systems in the shell-NAc modulates METH-induced enhancement of long term potentiation (LTP) in the hippocampus. Rats treated with METH (four injections of 5 mg/kg) exhibited enhanced LTP as compared to saline-treated animals. Intra-NAc infusion of muscimol (GABA receptor agonist) decreased METH-induced enhancement of dentate gyrus (DG)-LTP, while infusion of AP5 (NMDA receptor antagonist) prevented METH-induced enhancement of LTP. These data support the interpretation that reducing NAc activity can ameliorate METH-induced hippocampal LTP through a hippocampus-NAc-VTA circuit loop. Synapse 70:325-335, 2016.

KEYWORDS:

GABA transmission; dentate gyrus; glutamate transmission; long-term potentiation; methamphetamine; shell accumbens

PMID:
27029021
DOI:
10.1002/syn.21905
[Indexed for MEDLINE]

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