Inhibition of nitric oxide synthesis impairs rapid tolerance to ethanol

Khanna, J. M.; Morato, Gina Struffaldi; Shah, G.; Chau, A.; Kalant, H.

doi:10.1016/0361-9230(93)90317-5

Cited by 62 publications

(28 citation statements)

References 16 publications

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“…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: Abstract: Neuronal Nitric Oxide Synthase; Nnos; Nnos Splicementioning

confidence: 99%

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

confidence: 99%

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

et al. 2002

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“…Thus, inhibition of the development of tolerance to PCP cannot be attributed to some direct effect of L-NAME itself on motor performance. Khanna et al (1993) have reported that the administration of the NO synthase inhibitor N0-nitro-L-arginine, blocks the development of rapid tolerance to the motor incoordination induced by ethanol. Further, it has been reported that a NO synthase inhibitor prevents the development of tolerance to morphine (Kolesnikov et al, 1992).…”

Section: Resultsmentioning

confidence: 99%

“…NO is produced from L-arginine by NO syn-also been demonstrated in the mechanisms of synaptic plasticity, including long-term potentiation (LTP) in the hippocampus (O'Dell et al, 1991;Schuman & Madison, 1991), learning and memory (Chapman et al, 1992;Bohme et al, 1993;Hdlscher & Rose, 1993), tolerance to ethanol (Khanna et al, 1993), tolerance to the antinociceptive effect of morphine (Rauhala et al, 1994) and behavioural sensitization to cocaine (Pudiak & Bozath, 1993).…”

Section: Introductionmentioning

confidence: 99%

Role of nitric oxide in the development of tolerance and sensitization to behavioural effects of phencyclidine in mice

Noda

Yamada

Komori

et al. 1996

British J Pharmacology

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1 To determine whether nitric oxide (NO) was involved in tolerance and sensitization to the effects of phencyclidine (PCP), we examined NO synthase activity and the number of NADPH-diaphorase (NADPH-d)-positive cells in discrete brain regions of saline-, acute PCP-and repeated PCP-treated mice. We also investigated the effects of a NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on the behavioural changes induced by repeated PCP treatment in mice. 2 Acute PCP (1, 3, and 10 mg kg-', s.c.) treatment induced dose-dependent hyperlocomotion, motor incoordination and stereotyped behaviours, consisting of sniffing, head movement and ataxia in mice. 3 In mice treated repeatedly with PCP (1, 3, and 10 mg kg-' day-'), s.c., once a day for 14 days), the sniffing, head movement, ataxia and motor incoordination induced by PCP were attenuated (indicating the development of tolerance to these behaviours), whereas the hyperlocomotion induced by PCP was potentiated (indicating the development of sensitization to hyperlocomotion). The development of tolerance and sensitization to PCP-induced behaviours in the repeated PCP-treated mice was more marked at the dose of 10 mg kg-' day-') than at other doses. 4 NO synthase activity in the cerebral cortex and cerebellum, but not in the striatum and hippocampus, was significantly decreased by acute PCP (10 mg kg-') treatment in comparison with saline treatment, and such changes in activity in the cerebral cortex and cerebellum were reversed by repeated PCP treatment (10 mg kg-' day-'). 5 The number of neurones containing NADPH-d reactivity in the cerebral cortex, nucleus accumbens, and striatum of acute and repeated PCP-treated mice showed no change in comparison with salinetreated mice. 6 Tolerance to PCP (10 mg kg-' day-')-induced ataxia and motor incoordination was significantly attenuated by combined treatment with L-NAME (50 mg kg-' day-' i.p.). 7 Sensitization to PCP-induced hyperlocomotion was further enhanced by combined treatment with L-NAME (50 mg kg-' day-'). However, NG-nitro-D-arginine methyl ester (D-NAME, 50 mg kg-' day-', i.p.), a less active enantiomer of L-NAME, had no effect, suggesting a stereospecific mechanism. 8 The PCP-induced behaviours in animals that had exhibited tolerance and sensitization to PCP (10 mg kg-' day-') were not influenced by acute L-NAME (5 and 50 mg kg-', i.p.) or D-NAME (50 mg kg-', i.p.) treatment. 9 These results suggest that NO may play an important role in the development, but not in the maintenance, of tolerance and sensitization to the effects of PCP in mice.

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“…Constitutive and inducible forms of NOS have been identified, but it is the constitutive, Ca 2 ϩ -calmodulin-dependent form that is found in the brain and is hypothesized to be involved in the centrally mediated properties of nitric oxide (Lambert et al 1991). These central effects may include roles in memory formation (Chapman et al 1992;Yamada et al 1995), development of tolerance or sensitization to drugs of abuse (Khanna et al 1993;Kolesnikov et al 1992;Majeed et al 1994;Pudiak and Bozarth 1993), and response to stroke or neurotrauma (Nagafusi et al 1995;Schulz et al 1995).Although NOS is not completely co-localized with any known neurotransmitter, a subset of N-methyl-Daspartate (NMDA) neurons is associated with NOS (Garthwaite 1991). In these neurons, depolarization of the NMDA receptor by the endogenous excitatory amino acid neurotransmitter glutamate produces an influx of Ca 2 ϩ which binds to calmodulin.…”

mentioning

confidence: 99%

Nitric Oxide Synthase Inhibitors Attenuate Phencyclidine-Induced Disruption of Prepulse Inhibition

Wiley

1998

Neuropsychopharmacology

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Glutamate stimulation of N-methyl-D-aspartate (NMDA) receptors results in release of nitric oxide which may mediate the effects of NMDA receptor stimulation and ր or may result in feedback inhibition of the presynaptic neuron. Results of a previous study showed that nitric oxide synthase (NOS) inhibitors blocked dizocilpine-induced behavior in mice. In the present study, NOS inhibitors were tested in combination with phencyclidine (PCP),Nitric oxide is a soluble gas that is synthesized from the amino acid L -arginine by nitric oxide synthase (NOS). Nicotinamide-adenine dinucleotide phosphate-diaphorase (NADPH) is a required co-factor and citrulline is a co-product of the reaction. Constitutive and inducible forms of NOS have been identified, but it is the constitutive, Ca 2 ϩ -calmodulin-dependent form that is found in the brain and is hypothesized to be involved in the centrally mediated properties of nitric oxide (Lambert et al. 1991). These central effects may include roles in memory formation (Chapman et al. 1992;Yamada et al. 1995), development of tolerance or sensitization to drugs of abuse (Khanna et al. 1993;Kolesnikov et al. 1992;Majeed et al. 1994;Pudiak and Bozarth 1993), and response to stroke or neurotrauma (Nagafusi et al. 1995;Schulz et al. 1995).Although NOS is not completely co-localized with any known neurotransmitter, a subset of N-methyl-Daspartate (NMDA) neurons is associated with NOS (Garthwaite 1991). In these neurons, depolarization of the NMDA receptor by the endogenous excitatory amino acid neurotransmitter glutamate produces an influx of Ca 2 ϩ which binds to calmodulin. This Ca 2 ϩ -calmodulin complex activates NOS directly, resulting in a brief "puff" of nitric oxide that diffuses out of the presynaptic terminal and into astrocytic processes to ac- (Manzoni et al. 1992). Consistent with the dual role of nitric oxide at NMDA receptors, previous research has shown that, although drugs that inhibit nitric oxide (NOS inhibitors) share some behavioral effects with NMDA antagonists, they also may attenuate other behaviors associated with NMDA antagonism. Shared properties include anxiolytic effects, memory impairment, and phencyclidine (PCP)-like discriminative stimulus effects (Chapman et al. 1992;Jewett et al. 1996;Volke et al. 1997). In contrast, Deutsch et al. (1996) found that NOS inhibitors blocked "popping" behavior in mice that was induced by the PCP-like noncompetitive NMDA antagonist, dizocilpine. Exploration of the effects of NOS inhibitors on other behavioral effects of NMDA antagonists, so far, has been minimal.Another procedure in which PCP-like NMDA antagonists produce characteristic effects is prepulse inhibition of acoustic startle. The acoustic startle response is a reflexive movement that occurs upon abrupt presentation of a loud acoustic stimulus. Prepulse inhibition refers to a decrease in the magnitude of this startle response that is observed when the loud noise is preceded by a weak acoustic stimulus (a "prepulse"). Disruption of prepulse inhibition involves defici...

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Inhibition of nitric oxide synthesis impairs rapid tolerance to ethanol

Cited by 62 publications

References 16 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

Role of nitric oxide in the development of tolerance and sensitization to behavioural effects of phencyclidine in mice

Nitric Oxide Synthase Inhibitors Attenuate Phencyclidine-Induced Disruption of Prepulse Inhibition

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