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Implication of mGlu5 receptor in the enhancement of morphine-induced hyperlocomotion under chronic treatment with zolpidem
- Source :
- European journal of pharmacology. 738
- Publication Year :
- 2013
-
Abstract
- Long-term exposure to zolpidem induces drug dependence, and it is well known that the balance between the GABAergic and glutamatergic systems plays a critical role in maintaining the neuronal network. In the present study, we investigated the interaction between GABAA receptor α1 subunit and mGlu5 receptor in the limbic forebrain including the N.Acc. after treatment with zolpidem for 7 days. mGlu5 receptor protein levels were significantly increased after treatment with zolpidem for 7 days, and this change was accompanied by the up-regulation of phospholipase Cβ1 and calcium/calmodulin-dependent protein kinase IIα, which are downstream of mGlu5 receptor in the limbic forebrain. To confirm that mGlu5 receptor is directly involved in dopamine-related behavior in mice following chronic treatment with zolpidem, we measured morphine-induced hyperlocomotion after chronic treatment with zolpidem in the presence or absence of an mGlu5 receptor antagonist. Although chronic treatment with zolpidem significantly enhanced morphine-induced hyperlocomotion, this enhancement of morphine-induced hyperlocomotion was suppressed by treating it with the mGlu5 receptor antagonist MPEP. These results suggest that chronic treatment with zolpidem caused neural plasticity in response to activation of the mesolimbic dopaminergic system accompanied by an increase in mGlu5 receptor.
- Subjects :
- Male
STAT3 Transcription Factor
medicine.medical_specialty
Zolpidem
Time Factors
Tyrosine 3-Monooxygenase
medicine.drug_class
Pyridines
Phospholipase C beta
Receptors, Opioid, mu
Nucleus accumbens
Pharmacology
Motor Activity
Receptors, Metabotropic Glutamate
Receptors, N-Methyl-D-Aspartate
Glutamatergic
Mice
Prosencephalon
Internal medicine
medicine
Animals
GABA-A Receptor Agonists
RNA, Messenger
Receptor
Cyclic AMP Response Element-Binding Protein
Mice, Inbred ICR
Morphine
Chemistry
GABAA receptor
Glutamate Decarboxylase
musculoskeletal, neural, and ocular physiology
Dopaminergic
Receptor antagonist
Phosphoproteins
Receptors, GABA-A
Endocrinology
GABAergic
Calcium-Calmodulin-Dependent Protein Kinase Type 2
psychological phenomena and processes
Calcium-Calmodulin-Dependent Protein Kinase Type 4
medicine.drug
Subjects
Details
- ISSN :
- 18790712
- Volume :
- 738
- Database :
- OpenAIRE
- Journal :
- European journal of pharmacology
- Accession number :
- edsair.doi.dedup.....6513ee46816317448ac87b2ff04af9ed