Influence of nitric oxide synthase inhibition on the development of rapid tolerance to ethanol

Khanna, J. M.; Morato, Gina Struffaldi; Chau, A.; Shan, Guanqiao

doi:10.1016/0361-9230(95)00050-o

Cited by 30 publications

(19 citation statements)

References 27 publications

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“…It has been demonstrated that tolerance to the hypothermic effect of a single ethanol injection during administration of an equivalent dose 24 hr later occurs in mice (Crabbe et al, 1979). Interestingly, nNOS Ϫ/Ϫ mice did not develop rapid tolerance to ethanol-induced hypothermia, which is in line with a previous report showing that the NOS inhibitor L-nitroarginine blocked the development of rapid tolerance to the motor incoordinating effect of ethanol (Khanna et al, 1995). It is possible that the nNOS Ϫ/Ϫ mice showed high ethanol intake, less sensitivity to the sedative-hypnotic effects of ethanol, and no rapid tolerance to ethanol because of an increased rate of alcohol metabolism.…”

Section: Alcohol Sensitivity and Tolerance In Nnos ؊/؊ Micesupporting

confidence: 91%

“…Evidence from previous studies has implicated the nNOS-NO pathway in the modulation of CNSmediated drug effects. Thus, inhibition of NOS has been shown to influence the development of tolerance (Khanna et al, 1993(Khanna et al, , 1995Kolesnikov et al, 1993Kolesnikov et al, , 1997 and sensitization (Itzhak et al, 1998;Itzhak and Martin, 2000) to several drugs of abuse, including alcohol. Beside these findings, two other lines of evidence have prompted us to study the role of the nNOS gene in the regulation of neurobehavioral effects of alcohol:…”

Section: Abstract: Neuronal Nitric Oxide Synthase; Nnos; Nnos Splicementioning

confidence: 99%

“…This experiment was of interest because it has been proposed that initial sensitivity to ethanol can be negatively correlated with subsequent ethanol intake in humans (Schuckit, 1994;Schuckit and Smith, 1996), as well as in rodents (Thiele et al, 2000). Another phenomenon that often occurs in the course of chronic alcohol intake is tolerance, and it has been shown that NO formation is involved in the development of tolerance to ethanol (Khanna et al, 1993(Khanna et al, , 1995. Therefore, we also studied the induction of rapid tolerance to ethanol in nNOS knock-out mice.…”

Section: Abstract: Neuronal Nitric Oxide Synthase; Nnos; Nnos Splicementioning

confidence: 99%

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The Neuronal Nitric Oxide Synthase Gene Is Critically Involved in Neurobehavioral Effects of Alcohol

et al. 2002

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In the present study, we describe a new role of the neuronal nitric oxide synthase (nNOS) gene in the regulation of alcohol drinking behavior. Mice deficient in the nNOS gene (nNOS Ϫ/Ϫ) and wild-type control mice were submitted to a two-bottle free-choice procedure with either water or increasing concentrations of alcohol (2-16%) for 6 weeks. nNOS Ϫ/Ϫ mice did not differ in consumption and preference for low alcohol concentrations from wild-type animals; however, nNOS Ϫ/Ϫ mice consumed sixfold more alcohol from highly concentrated alcohol solutions than wild-type mice. Taste studies with either sucrose or quinine solutions revealed that alcohol intake in nNOS Ϫ/Ϫ and wild-type mice is associated, at least in part, with sweet solution intake but not with the taste of bitterness. When compared with wild-type mice, the nNOS Ϫ/Ϫ mice were found to be less sensitive to the sedative effects of ethanol as measured by shorter recovery time from ethanol-induced sleep and did not develop rapid tolerance to ethanol-induced hypothermia, although plasma ethanol concentrations were not significantly different from those of controls. Our findings contrast with previous reports that showed that nonselective NOS inhibitors decrease alcohol consumption. However, because alcohol consumption was suppressed in wild-type as well as nNOS Ϫ/Ϫ mice by the NOS inhibitor N G -nitro-L-arginine methyl ester, we conclude that the effect of nonselective NOS inhibitors on alcohol drinking is not mediated by nNOS. Other NOS isoforms, most likely in the periphery or other splice variants of the NOS gene, might contribute to the effect of nonselective NOS inhibitors on alcohol drinking. In summary, the nNOS gene is critically involved in the regulation of neurobehavioral effects of alcohol.

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Section: Alcohol Sensitivity and Tolerance In Nnos ؊/؊ Micesupporting

confidence: 91%

Section: Abstract: Neuronal Nitric Oxide Synthase; Nnos; Nnos Splicementioning

confidence: 99%

Section: Abstract: Neuronal Nitric Oxide Synthase; Nnos; Nnos Splicementioning

confidence: 99%

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The Neuronal Nitric Oxide Synthase Gene Is Critically Involved in Neurobehavioral Effects of Alcohol

et al. 2002

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“…Nitric oxide-related agents, i.e. nitric oxide donors and nitric oxide synthase inhibitors, influence ethanol narcosis (Adams et al 1994(Adams et al & 1995, consumption (Calapai et al 1996), tolerance (Khanna et al 1995) and withdrawal (Adams et al 1995;Uzbay et al 1997) and ethanol-induced organ damage (Lancaster 1995;Zou et al 1996).In our previous works nitric oxide synthase inhibitors, 7-nitroindazole and N G -nitro-L-arginine (L-NOARG) significantly increased the duration of ethanol (4 g/kg, intraperitoneally)-induced sleep. 7-Nitroindazole also slowed ethanol clearance after acute (at doses of 80 and 120 mg/ kg) and chronic administration (at a dose of 20 mg/kg) (Vassiljev et al 1998a).…”

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confidence: 94%

mentioning

confidence: 99%

The Influence of the Nitric Oxide Synthase InhibitorL‐NOARG on the Effects of Ethanol in Rats after Acute Ethanol Administration

Vassiljev¹,

Mesila²,

Väli³

et al. 2000

Pharmacology & Toxicology

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The aim of this work was to study the effects of the nitric oxide synthase inhibitor N G -nitro-L-arginine (L-NOARG) on the sedative and toxic effects of ethanol in rats. Ethanol at a dose of 3 g/kg, intraperitoneally induced sleep in rats (sleep time: 111.2∫10.3 min.). Administration of the nitric oxide synthase inhibitor L-NOARG (20 and 40 mg/ kg, intraperitoneally) 30 min. before ethanol significantly increased the duration of ethanol-induced sleep. L-NOARG at doses of 20 and 40 mg/kg reduced the exploratory activity of rats in the open-field test and significantly enhanced the sedative effect of ethanol in this test. It is possible that this effect is not caused by the interaction of ethanol with nitric oxide pathways but by synergistic CNS depression caused by ethanol and L-NOARG. L-NOARG (20 and 40 mg/kg) had no effect on ethanol concentrations in blood after acute ethanol administration (2 and 3 g/kg). Moreover, the combined administration of ethanol (2 g/kg) and L-NOARG (20 and 40 mg/kg) caused a decrease in the body weight of animals, observed for 14 days. Also, livers of these rats were studied for necrosis and connective tissue reaction. In histological studies L-NOARG at a dose of 40 mg/kg had no effect on hepatic necrosis caused by the acute administration of ethanol but strenghtened connective tissue reaction. L-NOARG is widely used in pharmacological studies, including those concerning the effects of ethanol. However, on the basis of our data the possibility of toxic interactions with ethanol should be considered.Nitric oxide, an unusual neurotransmitter molecule, is synthesized on demand by the enzyme nitric oxide synthase from its precursor L-arginine (Dawson & Dawson 1994). It has been proposed that some of the effects of ethanol are mediated through nitric oxide pathways (Adams et al. 1994). Nitric oxide-related agents, i.e. nitric oxide donors and nitric oxide synthase inhibitors, influence ethanol narcosis (Adams et al. 1994(Adams et al. & 1995, consumption (Calapai et al. 1996), tolerance (Khanna et al. 1995) and withdrawal (Adams et al. 1995;Uzbay et al. 1997) and ethanol-induced organ damage (Lancaster 1995;Zou et al. 1996).In our previous works nitric oxide synthase inhibitors, 7-nitroindazole and N G -nitro-L-arginine (L-NOARG) significantly increased the duration of ethanol (4 g/kg, intraperitoneally)-induced sleep. 7-Nitroindazole also slowed ethanol clearance after acute (at doses of 80 and 120 mg/ kg) and chronic administration (at a dose of 20 mg/kg) (Vassiljev et al. 1998a). 7-Nitroindazole attenuated the behavioural signs of ethanol withdrawal in mice due to pharmacokinetic interaction when administered immediately after the end of ethanol exposure (Vassiljev et al. 1998b). L-NOARG also significantly increased the toxicity of ethanol as evidenced by increased post-experimental lethality (Vassiljev et al. 1998a)

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Influence of drugs acting on nitric oxide-dependent pathways on ethanol tolerance in rats

Wazlawik

Morato

2003

Psychopharmacology

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The present results suggest that activation or inhibition of NO-dependent pathways increases or blocks rapid tolerance, respectively. These results give additional support to the hypothesis that brain NO plays a role in the development of tolerance to ethanol, but it remains to be confirmed if the same basic cellular mechanisms are also applicable to tolerance to other behavioural and/or physiological effects of this drug.

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Influence of nitric oxide synthase inhibition on the development of rapid tolerance to ethanol

Cited by 30 publications

References 27 publications

The Neuronal Nitric Oxide Synthase Gene Is Critically Involved in Neurobehavioral Effects of Alcohol

The Neuronal Nitric Oxide Synthase Gene Is Critically Involved in Neurobehavioral Effects of Alcohol

The Influence of the Nitric Oxide Synthase InhibitorL‐NOARG on the Effects of Ethanol in Rats after Acute Ethanol Administration

Influence of drugs acting on nitric oxide-dependent pathways on ethanol tolerance in rats

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