• Meriem Haddar, Kyosuke Uno, Kohei Hamatani, MuramatsuShin-IchiSIDivision of Neurological Gene Therapy, Open Inovation Center, Jichi Medical University, Shimotsuke, Japan.Center for Gene & Cell Therapy, Institute of Medical Science, The University of Tokyo, Tokyo, Japan., and Atsumi Nitta.
• Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
• Neuropsychopharmacol Rep. 2019 Sep 1; 39 (3): 209-216.

AimWe previously reported that methamphetamine (METH)-induced conditioned place preference was attenuated by Shati/Nat8l overexpression in the medial prefrontal cortex (mPFC). Shati/Nat8l overexpression in the mPFC expressed lower levels of both glutamate and dopamine (DA) in the nucleus accumbens (NAc) and attenuated METH-induced DA elevation. We suggested a mechanism in which a decline of glutamate levels in the NAc decreases extracellular DA levels. However, the hypothesis has not confirmed.MethodsWe conducted a recovery experiments by pre-microinjection of an mGluR group II antagonist, LY341495, into the NAc shell of mPFC-Shati/Nat8l-overexpressed mice followed by METH injection and DA levels measurement by in vivo microdialysis.ResultsPretreatment with LY341495 was able to restore METH-induced DA increase. Furthermore, mice injected with an adeno-associated virus vector containing GFP (AAV-GFP vector) in the mPFC expressed a colocalization of GFP with DARPP-32 a medium spiny neuron (MSN) marker. Next, co-immunostaining of DARPP-32 and neuronal nitric oxide synthase (nNOS: expressed in a subtype of gamma-Aminobutyric acid (GABA interneurons) in ventral tegmental area (VTA) showed a colocalization of nNOS and DARPP-32.ConclusionThese results provided a proof that Shati/Nat8l attenuation of METH-induced DA increase is mediated by mGluR group II in the NAc. Moreover, immunohistochemical study showed a direct connection of mPFC projection neurons with NAc MSN and a connection of MSN projection neurons with a subtype of GABA interneurons in VTA.© 2019 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd.

34 keywords...

hide…