Involvement of nitric oxide in intracerebroventricular β-endorphin-induced neuronal release of methionine-enkephalin

Hara, Shuichi; Kuhns, Eric R.; Ellenberger, Elizabeth A.; Mueller, Janet L.; Shibuya, Takeshi; Endo, Takahiko; Quock, Raymond M.

doi:10.1016/0006-8993(95)00065-x

Cited by 31 publications

(16 citation statements)

References 14 publications

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“…The neurochemical mediators through which inhaled N 2 O might increase peripheral blood flow could involve nitric oxide (NO), a potent vasodilator with an important role in blood flow distribution (69). A role for NO in N 2 Oaugmented heat dissipation seems plausible in part because Quock and colleagues (7,26,28) have implicated NO in other N 2 O effects, specifically its antinociceptive and anxiolytic effects. Additionally, because hypoxia-induced hypothermia is attenuated by microinjection of a NO synthesis inhibitor in the preoptic hypothalamus (65), it is possible that central as well as peripheral NO release could participate in mediating the hypothermic effect of N 2 O.…”

Section: Discussionmentioning

confidence: 99%

Assessment of heat production, heat loss, and core temperature during nitrous oxide exposure: a new paradigm for studying drug effects and opponent responses

Kaiyala¹,

Ramsay²

2005

American Journal of Physiology-Regulatory, Integrative and Comp

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Kaiyala, Karl J., and Douglas S. Ramsay. Assessment of heat production, heat loss, and core temperature during nitrous oxide exposure: a new paradigm for studying drug effects and opponent responses. Am J Physiol Regul Integr Comp Physiol 288: R692-R701, 2005. First published November 24, 2004; doi:10.1152/ajpregu. 00412.2004.-Studies using core temperature (T c) have contributed greatly to theoretical explanations of drug tolerance and its relationship to key features of addiction, including dependence, withdrawal, and relapse. Many theoretical accounts of tolerance propose that a given drug-induced psychobiological disturbance elicits opponent responses that contribute to tolerance development. This proposal and its theoretical extensions (e.g., conditioning as a mechanism of chronic tolerance) have been inferred from dependent variables, such as T c, which represent the summation of multiple underlying determinants. Direct measurements of determinants could increase the understanding of opponent processes in tolerance, dependence, and withdrawal. The proximal determinants of T c are metabolic heat production (HP) and heat loss (HL). We developed a novel system for simultaneously quantifying HP (indirect calorimetry), HL (direct gradient layer calorimetry), and T c (telemetry) during steady-state administrations of nitrous oxide (N 2O), an inhalant with abuse potential that has been previously used to study acute and chronic tolerance development to its hypothermia-inducing property. Rats were administered 60% N 2O (n ϭ 18) or placebo gas (n ϭ 16) for 5 h after a 2-h placebo baseline exposure. On average, N 2O rapidly but transiently lowered HP and increased HL, each by ϳ16% (P Ͻ 0.001). On average, rats reestablished and maintained thermal equilibrium (HP ϭ HL) at a hypothermic T c (Ϫ1.6°C). However, some rats entered positive heat balance (HP Ͼ HL) after becoming hypothermic such that acute tolerance developed, i.e., T c rose despite continued drug administration. This work is the first to directly quantify the thermal determinants of T c during administration of a drug of abuse and establishes a new paradigm for studying opponent processes involved in acute and chronic hypothermic tolerance development. addiction; drug tolerance; acute tolerance; drug dependence; gradient layer calorimetry; indirect calorimetry IN AN INFLUENTIAL 1971 REVIEW, Kalant et al. (32) made a convincing case for measuring drug tolerance using outcome variables that are continuously scaled, reliable, dose responsive, and amenable to analysis at the component level. An additional, desirable attribute is mediation by central regulatory mechanisms, reflecting the concept that drug use activates neuronal regulatory systems in ways that contribute to acute tolerance, chronic tolerance, withdrawal, drug dependence, and the potential for relapse in abstinent individuals (25,35,48,49,51,55,63). Core body temperature (T c ) epitomizes each of these attributes and has a long (59) and extensive history as an outcome variable in studies focus...

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Section: Discussionmentioning

confidence: 99%

Assessment of heat production, heat loss, and core temperature during nitrous oxide exposure: a new paradigm for studying drug effects and opponent responses

Kaiyala¹,

Ramsay²

2005

American Journal of Physiology-Regulatory, Integrative and Comp

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“…NOS inhibitors also attenuated the ability of i.c.v. administered ␤-endorphin to stimulate the neuronal release of methionineenkephalin in the rat spinal cord (Hara et al, 1995), suggesting that stimulated neuronal release of endogenous opioid peptides might be dependent on NO.…”

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confidence: 99%

Role of Nitric-Oxide Synthase Isoforms in Nitrous Oxide Antinociception in Mice

Ishikawa

Quock²

2003

J Pharmacol Exp Ther

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Exposure of mice to the anesthetic gas N 2 O evokes a prominent antinociceptive effect that is sensitive to antagonism by nonselective nitric-oxide synthase (NOS) inhibitors. The present study was conducted to identify whether a specific NOS isoform is implicated in N 2 O antinociception in mice. In the abdominal constriction test, exposure of mice to 25, 50, and 70% N 2 O resulted in a concentration-dependent antinociceptive effect that persisted for up to 6 min following removal of the mice from the N 2 O atmosphere into room air. This N 2 O antinociceptive effect was antagonized by pretreatment with S-methyl-Lthiocitrulline (SMTC) and higher doses of L-N 5 -(1-iminoethyl)-ornithine (L-NIO), which reportedly inhibit the neuronal and endothelial isoforms of NOS, respectively. Nevertheless, the N 2 O-induced antinociception was unaffected by pretreatment with low doses of either SMTC or L-NIO or by pretreatment with 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT), which selectively inhibits inducible NOS. The s.c. pretreatment with SMTC and L-NIO reduced brain NOS activity in a dose-dependent manner, whereas AMT had no such effect. Moreover, in blood pressure experiments, SMTC increased SBP in doseunrelated fashion, whereas L-NIO showed an appreciably weaker but dose-related increase in SBP. The i.c.v. pretreatment with SMTC also reduced N 2 O antinociception and brain NOS activity without increasing of SBP. These results suggest that it is the neuronal isoform of NOS that is involved in mediation of the antinociceptive effect of N 2 O in the mice.

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“…Since we have proposed in earlier investigations that N 2 O owes its antinociceptive effect in animals to stimulated neuronal release of endogenous opioid peptides (Branda et al, 2000;Cahill et al, 2000), the importance of the present findings is the localization of both opioid and NO mechanisms in the PAG of the midbrain. In as much as inhibition of NOS can significantly attenuate the increase in release of methionine-enkephalin in the rat spinal cord in response to centrally-administered β-endorphin (Hara et al, 1995), one explanation of these findings is that NO may play a key regulatory role in the N 2 O-stimulated neuronal release of endogenous opioid peptides that then activate opioid receptors in the PAG. Consistent with this hypothesis is our recent observation that exposure to N 2 O induces an NO-dependent increase in β-endorphin and NO metabolites in diasylate collected from the rat arcuate nucleus (Ohgami et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Nitrous oxide-antinociception is mediated by opioid receptors and nitric oxide in the periaqueductal gray region of the midbrain

Emmanouil

Dickens

Heckert

et al. 2008

European Neuropsychopharmacology

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Previous studies have shown that nitrous oxide (N 2 O)-induced antinociception is sensitive to antagonism by blockade of opioid receptors and also by inhibition of nitric oxide (NO) production. The present study was conducted to determine whether these occur within the same brain site. Mice were stereotaxically implanted with microinjection cannulae in the periaqueductal gray (PAG) area of the midbrain. In saline-pretreated mice, exposure to 70% N 2 O resulted in a concentrationdependent antinociceptive effect in the mouse abdominal constriction test. Pretreatment with an opioid antagonist in the PAG significantly antagonized the antinociceptive effect. Pretreatment with an inhibitor of NO production in the PAG also significantly antagonized the antinociceptive effect. These findings suggest that N 2 O acts in the PAG via an NO-dependent, opioid receptor-mediated mechanism to induce antinociception.

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Involvement of nitric oxide in intracerebroventricular β-endorphin-induced neuronal release of methionine-enkephalin

Cited by 31 publications

References 14 publications

Assessment of heat production, heat loss, and core temperature during nitrous oxide exposure: a new paradigm for studying drug effects and opponent responses

Assessment of heat production, heat loss, and core temperature during nitrous oxide exposure: a new paradigm for studying drug effects and opponent responses

Role of Nitric-Oxide Synthase Isoforms in Nitrous Oxide Antinociception in Mice

Nitrous oxide-antinociception is mediated by opioid receptors and nitric oxide in the periaqueductal gray region of the midbrain

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