کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
936690 | 1475179 | 2012 | 9 صفحه PDF | دانلود رایگان |
Evidence suggests that the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cGMP dependent protein kinase (PKG) signaling pathway plays a key role in memory processing, but the actual participation of this signaling cascade in the hippocampal CA1 during morphine-induced reward memory remains unknown. In this study, we investigated the role of the NO/sGC/PKG signaling pathway in the CA1 on morphine-induced reward memory using a conditioned place preference (CPP) paradigm. We found that rats receiving an intraperitoneal (i.p.) injection of 4 mg/kg morphine exhibited CPP, whereas rats treated with only 0.2 mg/kg morphine failed to produce CPP. Intra-CA1 injection of the neuronal NO synthase (nNOS) inhibitor 7-NI, the sGC inhibitor ODQ or the PKG inhibitor Rp-8-Br-PET-cGMPS had no effect on the acquisition of CPP by 4 mg/kg morphine. Intra-CA1 injection of 7-NI blocked the consolidation of CPP induced by 4 mg/kg morphine, and this amnesic effect of 7-NI was mimicked by ODQ and Rp-8-Br-PET-cGMPS. Intra-CA1 injection of the NOS substrate L-arg or the sGC activator YC-1 with an ineffective dose of morphine (0.2 mg/kg, i.p.) elicited CPP. This response induced by L-arg or YC-1 was reversed by pre-microinjection of Rp-8-Br-PET-cGMPS in the CA1. These results indicated that the activation of the NO/sGC/PKG signaling pathway in the CA1 is necessary for the consolidation of morphine-related reward memory.
► Rats receiving an injection of 4 mg/kg morphine exhibited CPP.
► Microinjection of 7-NI, ODQ or Rp-8-Br-PET-cGMPS blocked the consolidation of morphine CPP.
► Microinjection of L-arg or YC-1 with an ineffective dose of morphine elicited CPP.
► Pre-microinjection of Rp-8-Br-PET-cGMPS reversed this response induced by L-arg or YC-1.
Journal: Neurobiology of Learning and Memory - Volume 98, Issue 2, September 2012, Pages 130–138