Attenuation of morphine withdrawal signs by muscimol in the locus coeruleus of rats

Mirzaii‐Dizgah, Iraj; Karimian, Seyed Morteza; Hajimashhadi, Zahra; Riahi, Esmail; Ghasemi, Tayeb

doi:10.1097/fbp.0b013e3282fe8849

Cited by 17 publications

(11 citation statements)

References 29 publications

(36 reference statements)

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“…Others have demonstrated that non-selective pharmacological inactivation or lesions to the LC lessen morphine withdrawal symptoms, prevent footshock-evoked c-fos expression throughout the brain, and disrupt both unconditioned and conditioned aversive responses (Mirzaii-Dizgah et al, 2008; Neophytou et al, 2001; Passerin et al, 2000), but it has previously been untenable to selectively inhibit the activity of only these NE neurons and assess their role in stress-induced behaviors. To examine the role of LC-NE neurons in stress-induced anxiety-like behavior, we implemented a restraint stress paradigm, immediately followed by anxiety testing in the open field test (OFT) (Fig.…”

Section: Resultsmentioning

confidence: 99%

CRH Engagement of the Locus Coeruleus Noradrenergic System Mediates Stress-Induced Anxiety

McCall

Al‐Hasani

Siuda

et al. 2015

Neuron

535

483

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Summary The locus coeruleus noradrenergic (LC-NE) system is one of the first systems engaged following a stressful event. While numerous groups have demonstrated that LC-NE neurons are activated by many different stressors, the underlying neural circuitry and the role of this activity in generating stress-induced anxiety has not been elucidated. Using a combination of in vivo chemogenetics, optogenetics, and retrograde tracing we determine that increased tonic activity of the LC-NE system is necessary and sufficient for stress-induced anxiety and aversion. Selective inhibition of LC-NE neurons during stress prevents subsequent anxiety-like behavior. Exogenously increasing tonic, but not phasic, activity of LC-NE neurons is alone sufficient for anxiety-like and aversive behavior. Furthermore, endogenous corticotropin releasing hormone+ (CRH+) LC inputs from the amygdala increase tonic LC activity, inducing anxiety-like behaviors. These studies position the LC-NE system as a critical mediator of acute stress-induced anxiety and offer a potential intervention for preventing stress-related affective disorders.

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Section: Resultsmentioning

confidence: 99%

CRH Engagement of the Locus Coeruleus Noradrenergic System Mediates Stress-Induced Anxiety

McCall

Al‐Hasani

Siuda

et al. 2015

Neuron

535

483

View full text Add to dashboard Cite

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“…Likewise, various receptors and signaling molecules in the LC were demonstrated to be involved in the precipitation of withdrawal's somatic signs. Examples include alpha-2 adrenoceptors (Aghajanian, 1982; Engberg et al, 1982), GABA-A receptor (Mirzaii-Dizgah et al, 2008), glutamate transporters (Ozawa et al, 2004; Nakagawa and Satoh, 2004), and the cAMP pathway, including adenylyl cyclases 1 and 8 and cAMP response element-binding protein (Valverde et al, 2004; Oh et al, 2007; Zachariou et al, 2008; Han et al, 2006; Lane-Ladd et al, 1997). However, the role of the LC in the precipitation of somatic withdrawal signs remains somewhat debatable, given that lesioning of noradrenergic terminals arising from the LC does not inhibit the precipitation of physical symptoms of opioid withdrawal (Chieng and Christie, 1995).…”

Section: Discussionmentioning

confidence: 99%

Extracellular signal-regulated kinase activation in the amygdala mediates elevated plus maze behavior during opioid withdrawal

Hofford

Hodgson

Roberts³

et al. 2009

Behavioural Pharmacology

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This study examined whether activation of extracellular signal-regulated kinase (ERK) contributes to the increased open-arm time observed in the elevated plus maze (EPM) during opioid withdrawal. We applied SL327, a selective ERK kinase (MEK) inhibitor, to specific limbic areas and examined the effect on EPM behaviors of controls and during naloxone-precipitated morphine withdrawal. We next confirmed that ERK activation increased in limbic areas of mice undergoing naloxone-precipitated morphine withdrawal. Direct injection of SL327 into the amygdala blocked the withdrawal-induced increase in open-arm time; however, injecting SL327 into the septum had no effect. Consistent with these results, both 0.2 and 2 mg/kg naloxone increased ERK activation in the central amygdala of morphine-dependent mice. In drug-naïve mice, 2 mg/kg naloxone, but not 0.2 mg/kg, increased ERK activation in the central amygdala. During withdrawal, increased ERK activation was also observed in the lateral septum. In the LC, a significant increase was only observed in morphine-dependent mice receiving 2 mg/kg, but not 0.2 mg/kg, naloxone. It is concluded that ERK activation in limbic areas is likely involved in both the aversive properties of naloxone and in the affective/emotional symptoms of opioid withdrawal, including mediating EPM behaviors.

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“…Similar to the results of our study, administration of a GABA B agonist into the LC was shown to decrease withdrawal symptoms, while administration of a GABA B antagonist did not lead to any behavioural changes. Although microinjection of the GABA A agonist muscimol into the LC dose-dependently decreased withdrawal symptoms, GABA A and GABA B antagonists were reported to have no effect [26]. In some of the studies showing an effective suppressive action of drugs on morphine withdrawal, jumping behaviour was found to be affected in different ways - that is, increased [27], decreased [28] or not changed at all [29].…”

Section: Discussionmentioning

confidence: 99%

Effects of Injection of Gamma-Aminobutyric Acid Agonists into the Nucleus Accumbens on Naloxone-Induced Morphine Withdrawal

Topkara

Yananlı²,

Sakalli³

et al. 2017

Pharmacology

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Aims: This study was to investigate the effects of local administration of gamma-aminobutyric acid (GABA) agonists into the nucleus accumbens (NAc) on naloxone-induced morphine withdrawal symptoms. Methods: Bilateral guide cannulas were stereotaxically implanted in the shell or core regions of the NAc of Sprague-Dawley rats. After a recovery period, 3 morphine pellets, each consisting of 75 mg morphine base, were placed subcutaneously on the first and third days of the study with the rats under mild ether anaesthesia. The GABA agonists, baclofen hydrochloride or muscimol hydrobromide, were injected into the NAc, and morphine withdrawal was induced by naloxone on the fifth day. Results: Administration of baclofen to the shell or core regions of the NAc of Sprague-Dawley rats led to statistically significant decreases in both behavioural and locomotor activity parameters during the morphine withdrawal period, compared to the control group. However, there were no statistically significant changes in locomotor activity or withdrawal behavioural parameters, with the exception of wet dog shakes, between control and muscimol-treated groups. Conclusion: These findings show that GABAergic conduction in the NAc is effective on the morphine withdrawal symptoms, and that both the shell and core regions of the NAc are associated with this effect.

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Attenuation of morphine withdrawal signs by muscimol in the locus coeruleus of rats

Cited by 17 publications

References 29 publications

CRH Engagement of the Locus Coeruleus Noradrenergic System Mediates Stress-Induced Anxiety

CRH Engagement of the Locus Coeruleus Noradrenergic System Mediates Stress-Induced Anxiety

Extracellular signal-regulated kinase activation in the amygdala mediates elevated plus maze behavior during opioid withdrawal

Effects of Injection of Gamma-Aminobutyric Acid Agonists into the Nucleus Accumbens on Naloxone-Induced Morphine Withdrawal

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