The Prefrontal Cortex to the Hippocampus Glutamatergic Pathway Regulates Reward Effects of Methamphetamine

Author:

Zhao Dongdong,Shi Wenjing,Li Minyu,Xue Rui,Wang Hang,Zhang Le,Huang Mengbing,Bai Liping,Gu Rou,Li Ye,Zhang Xianwen,Kalivas Peter,Bai JieORCID

Abstract

AbstractMethamphetamine (METH) induces reward effects. The prefrontal cortex (PFC) plays a role in regulating top-down. The hippocampus is closely involved reward memory. However, the direct projects from the PFC to the hippocampus have not been studied well. Here, we use conditioned place preference (CPP), a recombinant adeno-associated virus 2/9 (rAAV2/9) and optogenetic approaches to explore a role in METH-CPP for a novel pathway projecting from the medial prefrontal prelimbic cortex (PrL) directly to the dorsal hippocampus CA1 (dCA1). Expressing CaMKIIα-ChR2 or CaMKIIα-eNpHR3.0 in the PrL and optically stimulating in the dCA1 blocks or enhances METH-CPP, respectively. Moreover, silencing the PrL to dCA1 glutamatergic pathway with tetanus neurotoxin (TeNT) enhances METH-CPP. These results identify a novel PrL-to-dCA1 glutamatergic pathway regulating METH-CPP.

Publisher

Cold Spring Harbor Laboratory

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