Shahed University

Silver nanoparticles (Ag-NPs) in the central amygdala protect the rat conditioned by morphine from withdrawal attack due to naloxone via high-level nitric oxide

Mahnaz Rahimpour | Manizheh Karami | Ali Haeri Rohani

Date :  2020/01/28
Publish in :    Naunyn-Schmiedebergs Archives of Pharmacology
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Keywords :Keywords Morphine . Naloxone . Silver nanoparticles . Withdrawal . CeA .NO

Abstract :
Abstract Repeated injection of morphine during conditioned place preference (CPP) leads to spatial craving due to high-level nitric oxide (NO) in the central nucleus of amygdala (CeA). Silver nanoparticles (Ag-NPs) can produce oxygen-free radicals that lead to NO formation. We aimed to show the Ag-NPs protective effect on naloxone (NLX)-induced morphine withdrawal in the conditioned rats. Wistar rats (300–350 g) were implanted with cannulae in the CeA. After recovery, they were randomly divided into experimental and saline groups. CPP was conducted by three-phase unbiased program. Morphine (0.5–7.5 mg/kg) was injected subcutaneously (s.c.) once/per day during the conditioning phase. Naloxone (NLX) (0.05–0.4 μg/rat) was given, intra-CeA, 10 min before the CPP test. Ag-NPs (0.0001–0.01 μg/rat) were administered alone or prior to the NLX effective dose (0.4 μg/rat), intra- CeA. Conditioning score and withdrawal signs (wet dog shaking and scratching) were obtained and compared with saline group data. All rats’ brains were collected in formalin 10 and after 48–72 h stained with NADPH-diaphorase, the NO marker. All data were analyzed by one-way or two-way ANOVA. Morphine (2.5–7.5 mg/kg, s.c.) induced a significant CPP vs. saline (1 mL/kg, s.c.). The single Ag-NPs had no significant effect, whereas the NLX caused meaningful WDS and scratching. However, the NLX pre-treatment in combination with Ag-NPs eliminated these signs. Furthermore, the NO level increased in the CeA. The Ag-NPs may protect the morphine-conditioned rats against the NLX-induced withdrawal symptoms due to high-level NO in the CeA.