The MEK inhibitor SL327 blocks acquisition but not expression of lithium-induced conditioned place aversion: a behavioral and immunohistochemical study

Longoni, R; Spina, Liliana; Vinci, Stefania; Acquas, Elio

doi:10.1007/s00213-011-2192-9

Cited by 22 publications

(16 citation statements)

References 55 publications

(87 reference statements)

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“…This effect could not be attributed to US or CS on their own. In particular, failure of US to elicit pERK expression in the PFCx is in agreement with previous studies showing that systemic lithium administration fails to affect ERK phosphorylation in mouse PFCx (Longoni et al, 2011); furthermore, the present results also indicate that sucrose consumption fails to affect ERK phosphorylation in PFCx (Figure 3) when measured 30 min after CS + exposure, overall suggesting that increased ERK phosphorylation in PFCx accompanies the learning of the CS-US association. This conclusion appears in agreement with the observation that CTA acquisition was also accompanied by increased phosphorylation of NR1 receptor subunit in the same area.…”

Section: Discussionsupporting

confidence: 93%

Acquisition and expression of conditioned taste aversion differentially affects extracellular signal regulated kinase and glutamate receptor phosphorylation in rat prefrontal cortex and nucleus accumbens

Fenu

Scheggi

Vinci

et al. 2014

Front. Behav. Neurosci.

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Conditioned taste aversion (CTA) can be applied to study associative learning and its relevant underpinning molecular mechanisms in discrete brain regions. The present study examined, by immunohistochemistry and immunocytochemistry, the effects of acquisition and expression of lithium-induced CTA on activated Extracellular signal Regulated Kinase (p-ERK) in the prefrontal cortex (PFCx) and nucleus accumbens (Acb) of male Sprague-Dawley rats. The study also examined, by immunoblotting, whether acquisition and expression of lithium-induced CTA resulted in modified levels of phosphorylation of glutamate receptor subunits (NR1 and GluR1) and Thr 34 -and Thr 75 -Dopamine-and-cAMP-Regulated PhosphoProtein (DARPP-32). CTA acquisition was associated with an increase of p-ERK-positive neurons and phosphorylated NR1 receptor subunit (p-NR1) in the PFCx, whereas p-GluR1, p-Thr 34 -and p-Thr 75 -DARPP-32 levels were not changed in this brain region. CTA expression increased the number of p-ERK-positive neurons in the shell (AcbSh) and core (AcbC) but left unmodified p-NR1, p-GluR1, p-Thr 34 -and p-Thr 75 -DARPP-32 levels. Furthermore, post-embedding immunogold quantitative analysis in AcbSh revealed that CTA expression significantly increased nuclear p-ERK immunostaining as well as p-ERK-labeled axo-spinous contacts. Overall, these results indicate that ERK and NR1, but not GluR1 and DARPP-32, are differentially phosphorylated as a consequence of acquisition and expression of aversive associative learning. Moreover, these results confirm that CTA represents an useful approach to study the molecular basis of associative learning in rats and suggest the involvement of ERK cascade in learning-associated synaptic plasticity.

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Section: Discussionsupporting

confidence: 93%

Acquisition and expression of conditioned taste aversion differentially affects extracellular signal regulated kinase and glutamate receptor phosphorylation in rat prefrontal cortex and nucleus accumbens

Fenu

Scheggi

Vinci

et al. 2014

Front. Behav. Neurosci.

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“…We have found that p-ERK is significantly upregulated immediately after morphine-induced CPP testing task whereas no change is found in rats without performing the task, suggesting that the drug craving may activate the ERK signal pathway. This observation was discrepant with a recent study which suggests that p-ERK is not critical for expression of lithiuminduced conditioned place aversion (Longoni et al 2011). The discrepancy may be due to the difference in the paradigm models.…”

Section: Discussionmentioning

confidence: 72%

The Activation of NMDA Receptor–ERK Pathway in the Central Amygdala is Required for the Expression of Morphine-Conditioned Place Preference in the Rat

Wang

Dai

et al. 2011

Neurotox Res

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Reinforcing effects of addictive drugs can be evaluated with the conditioned place preference (CPP) test which involves both the action of drugs and environmental cues. However, the encoded neural circuits and underlying signaling mechanism are not fully understood. In this study, we have used morphine-CPP model in the rat and characterized the role of N-methyl-D: -aspartate (NMDA) receptor and the phosphorylation of extracellular signal-regulated kinase (ERK) in the central nuclei of amygdala (CeA) in the expression of morphine-induced CPP. We have found that morphine repeated pairing treatment causes a significant preference for compartment paired with morphine after 1 day or 7 days post-training, which is associated with increased ERK1/2 phosphorylation (p-ERK1/2, a measure of ERK activity) in the CeA. More than 80% of the positive p-ERK1/2 neurons express NMDA receptor subunit NR1 by double immunofluorescence studies. The infusion of either MEK inhibitor U0126 or NMDA receptor antagonist MK-801 in the CeA not only suppresses the activation of ERK1/2 in the CeA but also abolishes the expression of CPP. These results suggest that the activation of the NMDA receptor-ERK signaling pathway in the CeA is required for the expression of morphine-induced place preference in the rat.

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“…As such, the affective properties of DREADD‐mediated DVC astrocyte activation remain unclear. A longer protocol may have revealed an effect since three or four conditioning sessions with LiCl does induce CPA in mice (Le Merrer et al, ; Longoni, Spina, Vinci, & Acquas, ; Sanjakdar et al, ; Zhang et al, ). We did, however, find that LiCl injection reduced locomotion during the conditioning trial while CNO treatment did not.…”

Section: Discussionmentioning

confidence: 99%

Regulation of food intake by astrocytes in the brainstem dorsal vagal complex

Macdonald

Holmes

Beall

et al. 2019

Glia

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A role for glial cells in brain circuits controlling feeding has begun to be identified with hypothalamic astrocyte signaling implicated in regulating energy homeostasis. The nucleus of the solitary tract (NTS), within the brainstem dorsal vagal complex (DVC), integrates vagal afferent information from the viscera and plays a role in regulating food intake. We hypothesized that astrocytes in this nucleus respond to, and influence, food intake. Mice fed high‐fat chow for 12 hr during the dark phase showed NTS astrocyte activation, reflected in an increase in the number (65%) and morphological complexity of glial‐fibrillary acidic protein (GFAP)‐immunoreactive cells adjacent to the area postrema (AP), compared to control chow fed mice. To measure the impact of astrocyte activation on food intake, we delivered designer receptors exclusively activated by designer drugs (DREADDs) to DVC astrocytes (encompassing NTS, AP, and dorsal motor nucleus of the vagus) using an adeno‐associated viral (AAV) vector (AAV‐GFAP‐hM3Dq_mCherry). Chemogenetic activation with clozapine‐N‐oxide (0.3 mg/kg) produced in greater morphological complexity in astrocytes and reduced dark‐phase feeding by 84% at 4 hr postinjection compared with vehicle treatment. hM3Dq‐activation of DVC astrocytes also reduced refeeding after an overnight fast (71% lower, 4 hr postinjection) when compared to AAV‐GFAP‐mCherry expressing control mice. DREADD‐mediated astrocyte activation did not impact locomotion. hM3Dq activation of DVC astrocytes induced c‐FOS in neighboring neuronal feeding circuits (including in the parabrachial nucleus). This indicates that NTS astrocytes respond to acute nutritional excess, are involved in the integration of peripheral satiety signals, and can reduce food intake when activated.

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The MEK inhibitor SL327 blocks acquisition but not expression of lithium-induced conditioned place aversion: a behavioral and immunohistochemical study

Abstract: These results indicate that pERK is critical for acquisition, but not expression, of lithium-induced CPA and that its activation in the dorsal striatum, during expression, is not critical for retrieval of the aversive memory.

Cited by 22 publications

References 55 publications

Acquisition and expression of conditioned taste aversion differentially affects extracellular signal regulated kinase and glutamate receptor phosphorylation in rat prefrontal cortex and nucleus accumbens

Acquisition and expression of conditioned taste aversion differentially affects extracellular signal regulated kinase and glutamate receptor phosphorylation in rat prefrontal cortex and nucleus accumbens

The Activation of NMDA Receptor–ERK Pathway in the Central Amygdala is Required for the Expression of Morphine-Conditioned Place Preference in the Rat

Regulation of food intake by astrocytes in the brainstem dorsal vagal complex

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