The role of nitric oxide in anticonvulsant and proconvulsant effects of morphine in mice

Homayoun, Houman; Khavandgar, Simin; Namiranian, Khodadad; Gaskari, Seyed Ali; Dehpour, Ahmad Reza

doi:10.1016/s0920-1211(01)00316-3

Cited by 94 publications

(66 citation statements)

References 48 publications

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“…As this effect was specific to those animals that had received morphine prior to training, the possibility of a state-dependent learning that had been associated with decreased NO should also be considered. Morphine and NO have diverse functional interactions in different neural processes that include both mediation and modification effects (Kolesnikov et al 1993;Brignola et al 1994;Homayoun et al 2002). Morphine may directly affect NO synthesis or exert functional interaction with NO through other neurotransmitter systems.…”

Section: Discussionmentioning

confidence: 99%

The effect of l-NAME and l-arginine on impairment of memory formation and state-dependent learning induced by morphine in mice

2003

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Rationale: Morphine and nitric oxide (NO) have important functional interactions in different neural processes, and both modulate learning and memory although their interaction in cognitive performance has not been elucidated. Objective: To examine the effect of the NO synthase (NOS) inhibitor N G -nitro-l-arginine methyl ester (l-NAME) and NOS substrate l-arginine on morphine-induced impairment of memory formation and the state-dependent retrieval of a passive avoidance task learned under morphine influence. Methods: All drugs were administered intraperitoneally, and a one-trial stepdown paradigm was used for the assessment of memory in adult male NMRI mice. Morphine was administered 30 min before training to induce impairment of memory formation and 30 min before test to induce statedependent retrieval of the memory acquired under pretraining morphine influence. l-NAME or l-arginine was administered either 5 min after training or 45 min before the test. Results: Pre-training morphine induced impairment of memory formation that was reversible by pre-test morphine but not saline. Post-training administration of larginine (200 mg/kg) and l-NAME (3, 10 and 30 mg/kg), respectively, facilitated and impaired the memory consolidation, but their pre-test injections did not affect retention. However, post-training l-arginine at per se noneffective doses of 20 mg/kg and 60 mg/kg reversed the morphine-induced impairment of memory formation. Pretest administration of l-NAME (3 mg/kg and 10 mg/kg) could restore the memory impairment induced by pretraining morphine, and this effect was blocked by concomitant pre-test l-arginine (60 mg/kg). Concomitant administration of low doses of l-NAME (1 mg/kg) and morphine (0.5 mg/kg) pre-test also revealed an additive effect in restoring the morphine state of memory.Conclusion: These results suggest that the impairment of memory formation and the facilitation of retrieval induced by morphine involves decreased synthesis/release of NO and can be counteracted by NOS substrate.

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Section: Discussionmentioning

confidence: 99%

The effect of l-NAME and l-arginine on impairment of memory formation and state-dependent learning induced by morphine in mice

2003

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“…However, posttraining administration of L -arginine can facilitate mem-ory formation and reverses the memory-impairing effects of the NOS inhibitor [15] . Furthermore, in recent years, a functional interaction between opioids and NO has been implicated in modulating analgesia [16] , tolerance and dependence [17,18] , thermoregulation [19] , seizure susceptibility [20] and morphine state-dependent learning [21] .…”

Section: Introductionmentioning

confidence: 99%

Morphine State-Dependent Learning Sensitization and Interaction with Nitric Oxide

et al. 2006

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In the present study, the effects of nitric oxide (NO) precursor L-arginine and L-NAME, a potent inhibitor of NO synthase (NOS), on the expression of sensitization of morphine were investigated. Pre-training administration of morphine (5 mg/kg) impaired memory retrieval compared to pre-training saline-treated animals. Amnesia due to pre-training morphine (5 mg/kg) was restored by pre-test morphine (5 mg/kg).The retrieval impairment was also inhibited in mice which had received once-daily injections of morphine (20 and 30 mg/kg, s.c.) for 3 days, followed by 5 days of no drug treatment before training (in order to induce morphine sensitization). Administration of L-arginine (60 mg/kg/day – 3 days) or L-NAME (20 mg/kg/day – 3 days) before training did not alter morphine state dependency. During acquisition of sensitization, administration of L-arginine (60 mg/kg) 20 min before morphine (10 mg/kg/day, for 3 days) increased, while injection of L-NAME (20 mg/kg) 20 min before morphine (30 mg/kg/day, for 3 days) decreased morphine state dependency. It is concluded that NO is involved in the morphine-induced sensitization.

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“…Acute subcutaneous administration of low doses (0.5-3 mg·kg −1 , s.c.) of morphine increased the threshold of seizures induced by pentylenetetrazole in mice, whereas high doses (15-60 mg·kg −1 ) of morphine had proconvulsant effects; L-NA or L-NAME inhibited both the anticonvulsant and proconvulsant effects of morphine, and L-arginine potentiated both effects, suggesting the involvement of the L-arginine/NO pathway in the modulation of seizure threshold by morphine [45]. There was evidence suggesting that melatonin enhanced both the anti-and proconvulsant effects of morphine via a mechanism that may involve the NO pathway [46].…”

Section: Convulsionmentioning

confidence: 92%

Interactions between morphine and nitric oxide in various organs

Toda¹,

Kishioka

Hatano

et al. 2009

J Anesth

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Nitric oxide (NO) plays obligatory roles as an important intercellular messenger in the control of physiological functions and it also participates in pathophysiological interventions. This labile, gaseous molecule is also involved in mechanisms underlying the beneficial and untoward actions of therapeutic agents. Endogenous NO is formed by endothelial and neurogenic NO synthases that are constitutively present mainly in the endothelium and nervous system, respectively, and is induced by lipopolysaccharides or cytokines mainly in mitochondria, glial cells, and vascular smooth muscle cells. NO modulates the effects of morphine on processes involving the central nervous system, such as learning, memory, convulsion, thermoregulation, and penile erection. This molecule is also involved in the modification of morphine actions on the cardiovascular, digestive, and respiratory systems. Morphine regulates NO bioavailability in various organs. NO formed by inducible NO synthase participates in some morphine actions in the immune system. Information concerning interactions between NO and morphine and other opioids in a variety of organs and tissues is quite useful in establishing new strategies for minimizing the noxious and unintended reactions that are frequently encountered during analgesic therapy.

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The role of nitric oxide in anticonvulsant and proconvulsant effects of morphine in mice

Cited by 94 publications

References 48 publications

The effect of l-NAME and l-arginine on impairment of memory formation and state-dependent learning induced by morphine in mice

The effect of l-NAME and l-arginine on impairment of memory formation and state-dependent learning induced by morphine in mice

Morphine State-Dependent Learning Sensitization and Interaction with Nitric Oxide

Interactions between morphine and nitric oxide in various organs

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