The interaction of morphine and γ-aminobutyric acid (GABA)ergic systems in anxiolytic behavior: using μ-opioid receptor knockout mice

Sasaki, Kenroh; Fan, Lir Wan; Tien, Lu Tai; Ma, Tangeng; Loh, Horace H.; Ho, Ing K.

doi:10.1016/s0361-9230(01)00785-7

Cited by 57 publications

(40 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It also supports the finding that systemic administration of opioid antagonists inhibits the anxiolytic properties of benzodiazepines in an anticonflict paradigm (Agmo et al, 1995;Yadin et al, 1991) and in the elevated plus maze (Agmo and Belzung, 1998). Although opioid receptor knockout animals commonly show changes in baseline behavior (Filliol et al, 2000;Sasaki et al, 2002), microinjection of NAL into the CeA in this set of experiments had no effect on baseline anxiety-related behaviors. These results indicate that the effects of NAL delivered into the CeA are selectively regulating the anxiolytic effects of diazepam.…”

Section: Discussionsupporting

confidence: 83%

Microinjection of Naltrexone into the Central, but not the Basolateral, Amygdala Blocks the Anxiolytic Effects of Diazepam in the Plus Maze

Burghardt

Wilson

2005

Neuropsychopharmacol

View full text Add to dashboard Cite

The amygdala is involved in behavioral and physiological responses to fear, and the anxiolytic properties of several drugs are localized to this region. Activation of endogenous opioid systems is known to occur in response to stress and a growing body of literature suggests that opioid systems regulate the properties of anxiolytic drugs. These experiments sought to elucidate the role of opioid receptors in the central (CeA) and basolateral (BLA) nuclei of the amygdala in regulating the anxiolytic properties of ethanol and diazepam. Male rats fitted with cannula received bilateral microinjections of the nonselective opioid receptor antagonist naltrexone (NAL) immediately followed by systemic delivery of either ethanol (1 g/kg) or diazepam (2 mg/kg) in the elevated plus maze. Both diazepam and ethanol decreased anxiety-like behavior. Delivery of NAL into the CeA blocked the anxiolytic properties of diazepam. Delivery of NAL into the BLA slightly increased open arm avoidance, but had no effect on the anxiolytic properties of diazepam. Microinjection of NAL into either nucleus failed to block the effects of ethanol. These results were specific to the anxiolytic properties of diazepam, since baseline behaviors were unaffected by microinjection of NAL. Microinjection of lidocaine produced results distinct from NAL and failed to block the anxiolytic actions of diazepam. These studies indicate distinct roles for opioid receptor systems in the CeA and BLA in regulating the anxiolytic properties of diazepam in the elevated plus maze. Further, opioid receptor systems in the CeA and BLA do not regulate the anxiolytic properties of ethanol in this test.

show abstract

Section: Discussionsupporting

confidence: 83%

Microinjection of Naltrexone into the Central, but not the Basolateral, Amygdala Blocks the Anxiolytic Effects of Diazepam in the Plus Maze

Burghardt

Wilson

2005

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…As with other anxiolytics, morphine's effects were dependent on the light level and familiarity of the testing situation during the social interaction task (Rogers and File, 1979). More consistent with our results, MOR-knockout mice show reduced anxiety-like behaviors in the elevated plus maze and light-dark box compared with wild-type controls (Sasaki et al, 2002;Filliol et al, 2000), although this knockout approach did not target changes in gene expression selectively to the CEA.…”

Section: Effects Of Mors In the Elevated Plus Mazesupporting

confidence: 87%

“…Imaging studies have demonstrated changes in MOR binding states during periods of negative affect in human volunteers (Zubieta et al, 2003), and MOR-knockout mice show reduced anxiety-like behaviors in the elevated plus maze and light-dark box compared with wild-type controls (Sasaki et al, 2002;Filliol et al, 2000). The local infusion of the MOR agonist morphine into the central amygdala has partial anxiolytic effects in the social interaction test (Rogers and File, 1979), whereas administration of an MOR antagonist into the basolateral region decreased time in the lit compartment of a light-dark transition test in mice (Narita et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

The Role of Amygdalar Mu-Opioid Receptors in Anxiety-Related Responses in Two Rat Models

Wilson

Junor

2008

Neuropsychopharmacol

View full text Add to dashboard Cite

Amygdala opioids such as enkephalin appear to play some role in the control of anxiety and the anxiolytic effects of benzodiazepines, although the opioid receptor subtypes mediating such effects are unclear. This study compared the influences of mu-opioid receptor (MOR) activation in the central nucleus of the amygdala (CEA) on unconditioned fear or anxiety-like responses in two models, the elevated plus maze, and the defensive burying test. The role of MORs in the anxiolytic actions of the benzodiazepine agonist diazepam was also examined using both models.

show abstract

“…In addition, it is known that morphine via opioid receptors exerts anxiolytic effects, probably by interacting with the dopaminergic system by suppressing GABA inhibitory input to dopamine neurons, thereby augmenting dopamine release. [19][20][21][22] As shown in the results, morphine at a high dose caused a decrease in REM sleep time. It is well known that cholinergic system is involved in REM sleep attenuation.…”

Section: Discussionsupporting

confidence: 63%

Effects of Anti-dementia Drugs on Morphine-Induced Somnolence

Ishida

Suga

Akagi

et al. 2009

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

It is well known that narcotics, such as morphine, fentanyl and oxycodone, have been used for patients with chronic pain. These narcotics cause several adverse effects; for example, somnolence, cognitive dysfunction, constipation and nausea. These adverse effects, especially somnolence, deteriorate the quality of life (QOL) of patients in the daytime.Morphine has high affinity for m, d and k receptors. On the other hand, it has been reported that opioid receptors were responsible for the sleep-wake cycle, [1][2][3][4] but there is little information about the effect of morphine on the sleepwake pattern; therefore, we tried to clarify the role of opioid receptors in the sleep-wake cycle by studying the characteristics of morphine in the sleep-wake pattern.Clinically, methylphenidate is used for the treatment of somnolence caused by opioid analgesics 5) ; however, drug dependence and tolerance were frequently observed during this drug therapy. On the other hand, it is recommended to use cholinesterase inhibitors for sedation or somnolence caused by narcotics in a clinical study 6) ; however, there is little evidence as to whether the above presumption is true or not. Donepezil is a centrally acting selective, competitive and reversible acetylcholinesterase inhibitor, widely used for the treatment of dementia. Moraes et al. 7) and we 8) reported that donepezil increased total times of wakefulness in human and animals, respectively. In addition, it has been reported that muscarinic and nicotinic acetylcholine receptors are responsible for the cognitive dysfunction caused by morphine in rats.9,10) N-Methyl-D-aspartic acid (NMDA) receptor antagonist, memantine, is also used for the treatment of dementia, which protects against neuronal death. From these findings, we presumed that anti-dementia drugs may be effective in not only cognitive dysfunction but also somnolence caused by narcotics.In the present study, therefore, we studied the characteristics of morphine in rat sleep patterns, and also the effects of donepezil and memantine on the somnolence caused by morphine in comparison with that of methylphenidate. MATERIALS AND METHODS AnimalsMale Wistar rats weighing 240-320 g (Japan SLC, Shizuoka) were used. All animals were maintained in an air-conditioned room with controlled temperature (24Ϯ2°C) and humidity (55Ϯ15%). They were housed in aluminum cages with sawdust and kept under a light-dark cycle (lights on from 07:00 to 19:00). The animals were allowed free access to food and water, except during the experiments. All procedures involving animals were conducted in accordance with the Guidelines for Animal Experiments at Okayama University Advanced Science Research Center.Surgery The animals were anesthetized with pentobarbital sodium (Nembutal 11) To record the electromyogram (EMG), stainless steel wire electrodes (200 mm) were implanted into the dorsal neck muscle. The electrodes were connected to a miniature receptacle and the whole assembly was fixed to the skull with dental cement. At least 7 d were allowed f...

show abstract

The interaction of morphine and γ-aminobutyric acid (GABA)ergic systems in anxiolytic behavior: using μ-opioid receptor knockout mice

Cited by 57 publications

References 20 publications

Microinjection of Naltrexone into the Central, but not the Basolateral, Amygdala Blocks the Anxiolytic Effects of Diazepam in the Plus Maze

Microinjection of Naltrexone into the Central, but not the Basolateral, Amygdala Blocks the Anxiolytic Effects of Diazepam in the Plus Maze

The Role of Amygdalar Mu-Opioid Receptors in Anxiety-Related Responses in Two Rat Models

Effects of Anti-dementia Drugs on Morphine-Induced Somnolence

Contact Info

Product

Resources

About