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Cross-talk between dopaminergic and noradrenergic systems in the rat ventral tegmental area, locus ceruleus, and dorsal hippocampus.
- Source :
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Molecular pharmacology [Mol Pharmacol] 2008 Nov; Vol. 74 (5), pp. 1463-75. Date of Electronic Publication: 2008 Aug 14. - Publication Year :
- 2008
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Abstract
- A decreased central dopaminergic and/or noradrenergic transmission is believed to be involved in the pathophysiology of depression. It is known that dopamine (DA) neurons in the ventral tegmental area (VTA) and norepinephrine (NE) neurons in the locus ceruleus (LC) are autoregulated by somatodendritic D(2)-like and alpha(2)-adrenoceptors, respectively. Complementing these autoreceptor-mediated inhibitory feedbacks, anatomical and functional studies have established a role for noradrenergic inputs in regulating dopaminergic activity, and reciprocally. In the present study, a microiontophoretic approach was used to characterize the postsynaptic catecholamine heteroreceptors involved in such regulations. In the VTA, the application of DA and NE significantly reduced the firing activity of DA neurons. In addition to a role for D(2)-like receptors in the inhibitory effects of both catecholamines, it was demonstrated that the alpha(2)-adrenoceptor antagonist idazoxan dampened the DA- and NE-induced attenuations of DA neuronal activity, indicating that both of these receptors are involved in the responsiveness of VTA DA neurons to catecholamines. In the LC, the effectiveness of iontophoretically applied NE and DA to suppress NE neuronal firing was blocked by idazoxan but not by the D(2)-like receptor antagonist raclopride, which suggested that only alpha(2)-adrenoceptors were involved. In the dorsal hippocampus, a forebrain region having a sparse dopaminergic innervation but receiving a dense noradrenergic input, the suppressant effects of DA and NE on pyramidal neurons were attenuated by idazoxan but not by raclopride. The suppressant effect of DA was prolonged by administration of the selective NE reuptake inhibitor desipramine and, to lesser extent, of the selective DA reuptake inhibitor 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)-piperazine (GBR12909), suggesting that both the NE and DA transporters were involved in DA uptake in the hippocampus. These findings might help in designing new antidepressant strategies aimed at enhancing DA and NE neurotransmission.
- Subjects :
- Adrenergic alpha-Antagonists pharmacology
Animals
Dopamine administration & dosage
Dopamine pharmacology
Hippocampus cytology
Idazoxan pharmacology
Iontophoresis methods
Locus Coeruleus cytology
Male
Neurons drug effects
Neurons physiology
Norepinephrine administration & dosage
Norepinephrine pharmacology
Rats
Rats, Sprague-Dawley
Ventral Tegmental Area cytology
Dopamine metabolism
Hippocampus metabolism
Locus Coeruleus metabolism
Norepinephrine metabolism
Ventral Tegmental Area metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1521-0111
- Volume :
- 74
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 18703671
- Full Text :
- https://doi.org/10.1124/mol.108.048033