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

Khavandgar, Simin; Homayoun, Houman; Zarrindast, Mohammad Reza

doi:10.1007/s00213-002-1377-7

Cited by 56 publications

(32 citation statements)

References 34 publications

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“…The effects of opioid receptor agonists (such as morphine) on state-dependent memory [26] , locomotor activity [27] , or oral stereotypy [28] have been previously demonstrated. According to our results, repeated morphine treatment followed by a 7-day (but not 24-hour) washout period significantly increased the effect of a test dose of morphine on locomotor activity and oral stereotypy.…”

Section: Discussionmentioning

confidence: 99%

Morphine-Induced Behavioral Sensitization Increased the mRNA Expression of NMDA Receptor Subunits in the Rat Amygdala

et al. 2008

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This study was designed to evaluate the effect of repeated morphine treatment on rat behavioral responses. In the genetic section, the mRNA expression of NMDA receptor subunits (NR1 and NR2A) was measured in certain areas of the male rat brain (striatum, prefrontal cortex, hippocampus, hypothalamus and amygdala). In the behavioral section, the effect of repeated morphine treatment on animal models such as locomotion, oral stereotypy, and state-dependent memory in a passive avoidance test was evaluated in the presence or absence of MK801 (NMDA receptor antagonist). Our results showed that chronic morphine treatment, followed by a 7-day (but not 24-hour) washout period, potentiated the effect of test doses of morphine, which is referred to as behavioral sensitization. Meanwhile, pretreatment of animals with MK801 (0.1 and 0.25 mg/kg), 30 min before a test dose of morphine (5 mg/kg), failed to attenuate the locomotion and oral stereotypy in the behavioral sensitization state. Interestingly, a higher dose of MK801 (0.25 mg/kg) decreased memory retrieval induced by morphine (2.5 mg/kg) in state-dependent memory. This effect may be due to the intrinsic motor enhancer property of higher doses of MK801, rather than the blockade of NMDA receptors. It can be concluded that MK801 does not affect morphine-induced behavioral sensitization in the expression phase. In the genetic section of the study, results of quantitative real-time RT-PCR clearly indicated that morphine sensitization increased the expression of NMDA receptor subunits mRNA in the amygdala (NR1 by 104% and NR2A by 85%), while the other areas of the brain were unaffected. Maenwhile, no change in the mRNA levels was observed in non-sensitized animals (chronic morphine treatment followed by a 24-hour washout period). In summary, the present study indicates that repeated morphine treatment followed by long-term (7-day washout) induces behavioral sensitization and causes a delayed increase in mRNA levels of NMDA receptor subunits in the rat amygdala. Meanwhile, it has previously been reported that the amygdala is involved in behavioral sensitization. Thus, it can be concluded that the increase in NMDA receptor expression is associated with morphine-induced behavioral sensitization.

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Section: Discussionmentioning

confidence: 99%

Morphine-Induced Behavioral Sensitization Increased the mRNA Expression of NMDA Receptor Subunits in the Rat Amygdala

et al. 2008

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“…injections the doses were adjusted so that each animal received a volume of at most 10 ml/ kg. Doses were selected from our previous study [21] . In order to induce sensitization to morphine, the animals received saline or different doses of morphine (10, 20 and 30 mg/kg, s.c.) once daily for 3 days (days 1-3) in the colony room, followed by 5 days (no drug treatment; days 4-8).…”

Section: Drug Treatmentmentioning

confidence: 99%

“…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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“…Several drugs have been demonstrated, in our laboratory and by other investigators, to replace the pre-testing effect of morphine on the restoration of memory, e.g. adenosine [19] , nitric oxide [20] , ␣ -adrenoceptor drugs [21] , K ATP channel modulators [22] , glucose and insulin [23] and ethanol [24] .…”

Section: Discussionmentioning

confidence: 99%

Influence of Intracerebroventricular Administration of Histaminergic Drugs on Morphine State-Dependent Memory in the Step-Down Passive Avoidance Test

Zarrindast¹,

Khalilzadeh²,

Rezayat³

et al. 2005

Pharmacology

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The effects of histaminergic drugs on morphine state-dependent memory of a passive avoidance task were examined in mice. Pre-training administration of morphine (5 mg/kg) led to state-dependent learning with impaired memory recall on the test day which was reversed by pre-test administration of the same dose of the opioid. The pre-test intracerebroventricular (i.c.v.) administration of the H₁ blocker (pyrilamine) prevented the restoration of memory by morphine. The H₂ blocker (ranitidine) was ineffective in this regard and the H₃ blocker (clobenpropit) potentiated the effect of morphine on memory recall. The pre-test i.c.v. administration of histamine alone (5, 10, and 20 µg/mouse) not only mimicked the effect of pre-test morphine treatment, but also increased this action of the opioid. The effect of histamine on memory recall was not changed by the pre-test administration of µ-opioid receptor antagonist, naloxone. In conclusion, the improvement of memory recall by morphine treatment, on the test day, seems to be, at least in part, through the release of histamine followed by the stimulation of H₁ receptors. Histamine by itself, when administered on the test day, mimicked morphine-induced memory improvement by a mechanism independent of the µ-opioid receptors.

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

Cited by 56 publications

References 34 publications

Morphine-Induced Behavioral Sensitization Increased the mRNA Expression of NMDA Receptor Subunits in the Rat Amygdala

Morphine-Induced Behavioral Sensitization Increased the mRNA Expression of NMDA Receptor Subunits in the Rat Amygdala

Morphine State-Dependent Learning Sensitization and Interaction with Nitric Oxide

Influence of Intracerebroventricular Administration of Histaminergic Drugs on Morphine State-Dependent Memory in the Step-Down Passive Avoidance Test

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