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

Hofford, Rebecca S.; Hodgson, Stephen R.; Roberts, Kris W.; Bryant, Camron D.; Evans, Christopher J.; Eitan, Shoshana

doi:10.1097/fbp.0b013e32832ec57e

Cited by 19 publications

(13 citation statements)

References 46 publications

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“…In the current report, we showed that mice undergoing NAL‐precipitated MOR withdrawal exhibit an increase in the time spent and entries to the open‐arms of the EPM in accordance with previous studies (Hodgson et al, ; Hofford et al, ; Lipták et al, ). The interpretation of these results is quite controversial but, a recent report by Lipták et al, () has shown that mice undergoing NAL‐precipitated MOR withdrawal spent significantly more time and traveled significantly more distance in the center of the open field compared to the control mice confirming the results observed in the EPM.…”

Section: Discussionsupporting

confidence: 93%

“…Thus, the EPM behaviors of withdrawn mice could indicate an increased motivation to scape that induces exploration and/or risk‐taking behaviors similar to the behaviors observed in addicts (Hodgson et al, ). Interestingly, all studies performed in mice show an anxiolitic‐like behavior during naloxone‐precipitated morphine withdrawal in the EPM test (Buckman et al, 2008; Hofford et al, ; Lipták et al, ). However, studies performed in rats (Zhang et al, 2008) show an anxiety‐like behavior.…”

Section: Discussionmentioning

confidence: 99%

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Baclofen prevents the elevated plus maze behavior and BDNF expression during naloxone precipitated morphine withdrawal in male and female mice

Pedrón

Varani

Balerio

2016

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In previous studies we have shown that baclofen, a selective GABAB receptor agonist, prevents the somatic expression and reestablishes the dopamine and μ-opioid receptors levels, modified during naloxone-precipitated morphine withdrawal syndrome in male and female mice. There are no previous reports regarding sex differences in the elevated plus maze (EPM) and the expression of BDNF in morphine-withdrawn mice. The present study analyses the behavioral and biochemical variations during morphine withdrawal in mice of both sexes, and whether these variations are prevented with baclofen. Swiss-Webster albino prepubertal mice received morphine (2 mg/kg, i.p.) twice daily, for 9 consecutive days. On the 10th day, one group of morphine-treated mice received naloxone (opioid receptor antagonist; 6 mg/kg, i.p.) 1 h after the last dose of morphine to precipitate withdrawal. A second group received baclofen (2 mg/kg, i.p.) before naloxone administration. The EPM behavior was measured during 15 min after naloxone injection. The expression of BDNF-positive cells was determined by immunohistochemistry. Withdrawn male mice showed a higher percentage of time spent and number of entries to the open arms compared to withdrawn female mice. Baclofen prevented this behavior in both sexes. BDNF expression decreased in the AcbC, BNST, CeC, and CA3 of the hippocampus while increased in the BLA of morphine withdrawn male. Baclofen pretreatment prevented the BDNF expression observed in morphine withdrawn male mice in all the brain areas studied except in the CeC. Baclofen prevention of the EPM behavior associated to morphine withdrawal could be partially related to changes in BDNF expression.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Baclofen prevents the elevated plus maze behavior and BDNF expression during naloxone precipitated morphine withdrawal in male and female mice

Pedrón

Varani

Balerio

2016

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“…Moreover, ERK 1/2 inhibitors can attenuate the analgesic effect evoked by morphine [29,30] and block the increased open arm-time after morphine withdrawal on EPM [31]. There is no data about the effect of obestatin on ERK 1/2 pathway in the central nervous system after in vivo treatment, but obestatin might exert its effect on mild morphine withdrawal and analgesia via regulation of ERK 1/2 pathway.…”

Section: Discussionmentioning

confidence: 91%

Obestatin prevents analgesic tolerance to morphine and reverses the effects of mild morphine withdrawal in mice

Lipták

Dochnal

Csabafi

et al. 2013

Regulatory Peptides

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Obestatin is a 23-amino acid gut-derived neuropeptide, encoded by the same gene with ghrelin. The goal of this study was to examine the effects of obestatin on the acute and chronic analgesic actions of morphine and on mild morphine withdrawal. Open-field (OF) and elevated plus maze (EPM) tests were used to assess mild morphine withdrawal-induced behavior changes and the heat-radiant tail-flick assay was used to investigate analgesic actions of morphine. CFLP male mice were treated twice a day with graded doses of morphine in EPM and OF experiments and once a day in tail-flick studies. Obestatin (1.5 μg/2 μl) was administrated once a day in all experiments. Furthermore, 0.2 mg/kg naloxone or saline was administered after the final injection of morphine at a dose of 20 mg/kg in EPM and OF. These behavioral parameters were monitored in the OF: the percentage of center ambulation time and distance; whereas in the EPM: the time spent in open arms and the entries into open arms compared to the total time (%OAT) and entries (%OAE). In the OF, obestatin significantly decreased the percentage of time spent in the center in mice undergoing naloxone-precipitated mild morphine withdrawal. EPM results were similar to open field, but obestatin had no significant effect on parameters mentioned above. Besides, obestatin maintained the analgesic effect of morphine 90 and 120 min after morphine injection in mice treated with morphine receiving obestatin compared to mice treated with morphine. In tolerance studies, obestatin diminished the analgesic tolerance to morphine on the 5th day. In this study we confirmed that obestatin reversed the effect of mild morphine withdrawal and enhances the analgesic effect of morphine. These data suggest that obestatin may have a role in opioid-induced analgesia and in behavioral responses induced by opioid withdrawal.

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“…Recently, reports have implicated ERK 1/2 signal transduction in morphine reward and plasticity including place preference and psychomotor sensitization (134; 135) . ERK 1/2 activity in the amygdala was also found to mediate anxiety-like behaviors during morphine withdrawal (136) . Together, these reports strongly support the concept that ERK 1/2 signaling is an essential mediator of μ-opioid-induced plasticity in the brain and spinal cord.…”

Section: Opioid Signaling and Behaviormentioning

confidence: 99%

Molecular Mechanisms of Opioid Receptor-dependent Signaling and Behavior

2011

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Opioid receptors have been targeted for the treatment of pain and related disorders for thousands of years, and remain the most widely used analgesics in the clinic. Mu (μ), kappa (κ), and delta (δ) opioid receptors represent the originally classified receptor subtypes, with opioid receptor like-1 (ORL1) being the least characterized. All four receptors are G-protein coupled, and activate inhibitory G-proteins. These receptors form homo- and hetereodimeric complexes, signal to kinase cascades, and scaffold a variety of proteins. In this review, we discuss classical mechanisms and developments in understanding opioid tolerance, opioid receptor signaling, and highlight advances in opioid molecular pharmacology, behavioral pharmacology, and human genetics. We put into context how opioid receptor signaling leads to the modulation of behavior with the potential for therapeutic intervention. Finally, we conclude that there is a continued need for more translational work on opioid receptors in vivo.

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

Cited by 19 publications

References 46 publications

Baclofen prevents the elevated plus maze behavior and BDNF expression during naloxone precipitated morphine withdrawal in male and female mice

Baclofen prevents the elevated plus maze behavior and BDNF expression during naloxone precipitated morphine withdrawal in male and female mice

Obestatin prevents analgesic tolerance to morphine and reverses the effects of mild morphine withdrawal in mice

Molecular Mechanisms of Opioid Receptor-dependent Signaling and Behavior

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