Neuroscience 2004 Abstract
| Presentation Number: | 163.1 |
|---|---|
| Abstract Title: | Dopamine D4 receptor activation induces immediate early gene expression and map kinase phosphorylation. |
| Authors: |
Bitner, R.*1
; Nikkel, A. L.1
; Otte, S.1
; Bhatia, P.1
; Cowart, M. D.1
; Stewart, A.1
; Decker, M. D.1
; Brioni, J. D.1
; Moreland, R. B.1
14N5 Bldg AP9A, Abbott Labs, Abbott Park, IL |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - G-Protein linked Receptors -- Catecholamine receptors |
| Secondary Theme and Topics | Synaptic Transmission and Excitability<br />- Neurotransmitters<br />-- Catecholamines |
| Session: |
163. G-Protein-Linked Catecholamine Receptors: Pharmacology Poster |
| Presentation Time: | Sunday, October 24, 2004 8:00 AM-9:00 AM |
| Location: | San Diego Convention Center - Hall A-H, Board # I12 |
| Keywords: | c-Fos, ERK, hypothalamus, antagonist |
The dopamine D4 receptor is widely distributed in the CNS, particularly in limbic structures such as the prefrontal cortex and hippocampus. As a D2-like dopamine receptor, the D4 subtype is classified a Gi/Go protein coupled receptor and therefore considered as an inhibitor of neuronal firing. We previously reported that the selective D4 agonist PD168077 induces expression of the immediate early gene (IEG) c-Fos and phosphorylation of MAP kinase ERK1/2 in the hypothalamic paraventricular nucleus (PVN) (Otte et al., 2003, SFN Abstracts), a region associated with sexual behavior mediated by D4 receptor transmission. In the present studies, we immunohistochemically examined the ability of a novel, selective D4 antagonist A-381393 (presented at this meeting) to block c-Fos induction and ERK1/2 phosphorylation produced by the D4 agonist PD168077 in the rat PVN. Pretreatment with A-381393 (10 ìmol/kg s.c.) prevented the induction of c-Fos seen with PD168077 (1ìmol/kg s.c.) treatment alone and significantly reduced (>50%) the amount of Fos immunoreactivity as compared to vehicle-treated controls. A similar reduction in “basal” Fos expression was observed in the PVN of rats treated with the D4 antagonist alone. A-381393 also blocked the ability of PD168077 to increase ERK1/2 phosphorylation, as did an inhibitor of ERK1/2 phosphorylation, SL327 (100 mg/kg i.p.). Our results further demonstrate the functional expression of dopamine D4 expression in the PVN linked to signal transduction pathways that include IEG and MAP kinase activation. Moreover, the ability of the selective D4 antagonist A-381393 alone to reduce Fos expression below levels seen in control rats suggests the presence of a tonic D4 receptor activation under basal conditions in vivo. (Supported by Abbott Labs).
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2004 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2004. Online.
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