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Effects of chronic desipramine treatment on alpha2-adrenoceptors and mu-opioid receptors in the guinea pig cortex and hippocampus.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2008 Jan 28; Vol. 579 (1-3), pp. 116-25. Date of Electronic Publication: 2007 Oct 11. - Publication Year :
- 2008
-
Abstract
- The existence of a close relation between presynaptic inhibitory alpha(2)-adrenoceptor and mu-opioid receptor pathways is well established. Such interplay may occur during chronic conditions that give rise to neuroadaptive changes involving both receptor systems. The aim of this study was to examine the effect of chronic treatment with the tricyclic antidepressant drug, desipramine, on alpha(2)-adrenoceptors and mu-opioid receptors in the guinea pig brain. Guinea pigs were treated with 10 mg/kg desipramine, injected i.p. for 21 days, every 24 h. The levels of expression of alpha(2)-adrenoceptors and mu-opioid receptors, the G protein receptor regulatory kinase, GRK2/3 and signal transduction inhibitory G proteins in synaptosomes of the guinea pig hippocampus and cortex were evaluated by immunoblotting. Quantitative analysis of alpha(2)-adrenoceptor and mu-opioid receptor mRNA levels has been carried out by competitive reverse transcriptase polymerase chain reaction. The expression levels of alpha(2)-adrenoceptors and mu-opioid receptors and the respective mRNAs were found unchanged in the cortex, after chronic desipramine treatment. In these experimental conditions alpha(2)-adrenoceptor and mu-opioid receptor levels decreased, while the relevant transcripts increased, in the hippocampus. GRK2/3 levels remained unchanged and increased, respectively, in the cortex and the hippocampus, after chronic exposure to desipramine. In the same experimental conditions, Galpha(i1), Galpha(i2), Galpha(o) and Galpha(z) levels remained unchanged, while Galpha(i3) levels decreased, in the cortex; whereas, Galpha(i1), Galpha(i2) and Galpha(i3) levels significantly increased, and Galpha(o) and Galpha(z) levels remained unchanged, in the hippocampus. On the whole, the present data suggest that alpha(2)-adrenoceptor and mu-opioid receptor expression and transcription are similarly influenced by chronic treatment with desipramine, in the guinea pig cortex and hippocampus. Furthermore, alterations in the levels of regulatory GRK2/3 and of inhibitory signal transduction G proteins, relevant to activation of both receptor pathways, have been documented. The distinct pattern of adaptations of the different protein studied in response to chronic desipramine treatment in both regions is discussed.
- Subjects :
- Adrenergic Uptake Inhibitors administration & dosage
Animals
Antidepressive Agents, Tricyclic administration & dosage
Cerebral Cortex drug effects
Cerebral Cortex metabolism
Desipramine administration & dosage
G-Protein-Coupled Receptor Kinase 2 drug effects
G-Protein-Coupled Receptor Kinase 2 metabolism
G-Protein-Coupled Receptor Kinase 3 drug effects
G-Protein-Coupled Receptor Kinase 3 metabolism
GTP-Binding Protein alpha Subunits drug effects
GTP-Binding Protein alpha Subunits metabolism
Gene Expression Regulation drug effects
Guinea Pigs
Hippocampus drug effects
Hippocampus metabolism
Male
RNA, Messenger drug effects
RNA, Messenger metabolism
Receptors, Adrenergic, alpha-2 metabolism
Receptors, Opioid, mu metabolism
Reverse Transcriptase Polymerase Chain Reaction
Synaptosomes metabolism
Adrenergic Uptake Inhibitors pharmacology
Antidepressive Agents, Tricyclic pharmacology
Desipramine pharmacology
Receptors, Adrenergic, alpha-2 drug effects
Receptors, Opioid, mu drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2999
- Volume :
- 579
- Issue :
- 1-3
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 18028907
- Full Text :
- https://doi.org/10.1016/j.ejphar.2007.10.007