11 research outputs found
Involvement of nitric oxide in granisetron improving effect on scopolamine-induced memory impairment in mice
AbstractGranisetron, a serotonin 5-HT3 receptor antagonist, widely used as an antiemetic drug following chemotherapy, has been found to improve learning and memory. In this study, effects of granisetron on spatial recognition memory and fear memory and the involvement of nitric oxide (NO) have been determined in a Y-maze and passive avoidance test. Granisetron (3, 10mg/kg, intraperitoneally) was administered to scopolamine-induced memory-impaired mice prior to acquisition, consolidation and retrieval phases, either in the presence or in the absence of a non-specific NO synthase inhibitor, l-NAME (3, 10mg/kg, intraperitoneally); a specific inducible NO synthase (iNOS) inhibitor, aminoguanidine (100mg/kg); and a NO precursor, l-arginine (750mg/kg). It is demonstrated that granisetron improved memory acquisition in a dose-dependent manner, but it was ineffective on consolidation and retrieval phases of memory. The beneficial effect of granisetron (10mg/kg) on memory acquisition was significantly reversed by l-NAME (10mg/kg) and aminoguanidine (100mg/kg); however, l-arginine (750mg/kg) did not potentiate the effect of sub-effective dose of granisetron (3mg/kg) in memory acquisition phase. It is concluded that nitric oxide is probably involved in improvement of memory acquisition by granisetron in both spatial recognition memory and fear memory.This article is part of a Special Issue entitled The Cognitive Neuroscience
Nitric Oxide Mediates Effects of Acute, not Chronic Naltrexone on LPS-Induced Hepatic Encephalopathy in Cirrhotic Rats
Recent studies suggest endogenous opioids and nitric oxide (NO) are involved in the pathophysiology of hepatic encephalopathy (HE). In this study, the interaction between the opioid receptors antagonist, and NO was investigated on lipopolysaccharide (LPS)-induced HE in cirrhotic rats. Male rats were divided in the sham- and bile duct ligation (BDL)-operated groups. Animals treated with saline; naltrexone (10 mg/kg, i.p.); L-NAME (3 mg/kg, i.p.); alone or in combination by naltrexone. To induce HE, LPS (1 mg/kg, i.p.) was injected one hour after the final drug treatment. Hepatic encephalopathy scoring, hepatic histology and plasma NO metabolites levels and mortality rate were recorded. Deteriorated level of consciousness and mortality after LPS administration significantly ameliorated following both acute- and chronic treatment with naltrexone in cirrhotic rats. While, acute- and chronic administration of L-NAME did not change hepatic encephalopathy scores in cirrhotic rats. The effects of acute- but not chronic treatment of naltrexone on hepatic encephalopathy parameters were reversed by L-NAME. Plasma NOx concentrations elevated in BDL rats, which were decreased after acute- and chronic treatment by naltrexone or L-NAME, significantly. We suggest both acute, and chronic treatment with naltrexone improved LPS-induced HE. But, only acute treatment with naltrexone may affect through NO pathway.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author
HIV-1 and cocaine disrupt dopamine reuptake and medium spiny neurons in female rat striatum.
HIV-1 and addictive drugs, such as cocaine (COC), may act in combination to produce serious neurological complications. In the present experiments, striatal brain slices from HIV-1 transgenic (Tg) and F344 control female rats were studied. First, we examined dopamine (DA) reuptake in control, HIV-1, COC-treated (5µM) and HIV-1+COC-treated, striatal slices using fast scan cyclic voltammetry. COC-treated striatal slices from F344 control animals significantly increased DA reuptake time (T80), relative to untreated control slices. In contrast, in HIV-1 Tg striatal slices, DA reuptake time was extended by HIV-1, which was not further altered by COC treatment. Second, analysis of medium spiny neuronal populations from striatal brain slices found that controls treated with cocaine displayed increases in spine length, whereas cocaine treated HIV-1 slices displayed decreased spine length. Taken together, the current study provides evidence for dysfunction of the dopamine transporter (DAT) in mediating DA reuptake in HIV-1 Tg rats and limited responses to acute COC exposure. Collectively, dysfunction of the DAT reuptake and altered dendritic spine morphology of the MSNs, suggest a functional disruption of the dopamine system within the HIV-1 Tg rat
Cocaine differentially alters dendritic spine length.
<p>An acute exposure of striatal drug slices to drug challenge was used to determine the neuroplastic response to cocaine. <b>(A-B)</b> Relative frequency distributions of dendritic spine length of the MSNs of the nucleus accumbens as a function of cocaine treatment. Length of dendritic spines of the MSNs in the nucleus accumbens increase in the control condition when exposed to cocaine (H(3) = 8.9, N = 17, p<sub>adj</sub>≤0.05); cocaine exposure of HIV-1 Tg MSNs were significantly shifted to shorter spines as a function of cocaine treatment. n = 4–5 animals/group, 1–2 neurons/animal were counted per animal yielding a total of 4,941 spines for analysis of the effect of cocaine in the slices from the F344/N group and a total of 4,708 spines or analysis of the effect of cocaine in the slices from the HIV-1 transgenic group.</p
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Binge-like acquisition of α-pyrrolidinopentiophenone (α-PVP) self-administration in female rats
RationaleThe synthetic cathinone α-pyrrolidinopentiophenone (α-PVP) has been associated with bizarre public behavior in users. Association of such behavior with extended binges of drug use motivates additional investigation, particularly since a prior study found that half of male rats experience a binge of exceptionally high intake, followed by sustained lower levels of self-administration during the acquisition of intravenous self-administration (IVSA) of a related drug, 3,4-methylenedioxypyrovalerone.ObjectivesThe binge-like acquisition pattern is novel for rat IVSA; thus, the present study sought to determine if this effect generalizes to IVSA of α-PVP in female rats.MethodsFemale Wistar rats were trained in IVSA of α-PVP (0.05 mg/kg/inf) in experimental chambers containing an activity wheel. Groups were trained with the wheels fixed (No-Wheel group), fixed for the initial 5 days of acquisition or free to move throughout acquisition (Wheel group). The groups were next subjected to a wheel access switch and then all animals to dose-substitution (0.0125-0.3 mg/kg/inf) with the wheels alternately fixed and free to move.ResultsApproximately half of the rats initiated their IVSA pattern with a binge day of exceptionally high levels of drug intake, independent of wheel access condition. Wheel activity was much lower in the No-Wheel group in the wheel switch post-acquisition. Dose-effect curves were similar for wheel access training groups, for binge/no binge phenotypic subgroups and were not altered with wheel access during the dose-substitution.ConclusionThis confirms the high reinforcer effectiveness of α-PVP in female rats and the accompanying devaluation of wheel activity as a naturalistic reward