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Inhibition of VTA neurons activates the centrally projecting Edinger-Westphal nucleus: evidence of a stress-reward link? - PubMed

Inhibition of VTA neurons activates the centrally projecting Edinger-Westphal nucleus: evidence of a stress-reward link?

Andrey E Ryabinin et al. J Chem Neuroanat. 2013 Dec.

Abstract

The primary site of urocortin 1 (Ucn1) expression in the brain is the centrally projecting Edinger-Westphal nucleus. The EWcp is innervated by dopaminergic neurons of the ventral tegmental area (VTA). To investigate whether activity of EWcp is regulated by the VTA, we investigated the effects of local pharmacological inhibition of VTA activity on the induction of Fos immunoreactivity in the EWcp of male C57BL/6J mice. A unilateral intracranial administration of the GABA agonist muscimol aimed at the VTA resulted in increased number of Fos-positive cells in the EWcp. This induction was lower than that produced by an intraperitoneal injection of 2.5 g/kg of ethanol. To investigate whether inhibition of dopaminergic neurons was responsible for induction of Fos, a second experiment was performed where the dopamine agonist quinpirole was unilaterally injected targeting the VTA. Injections of quinpirole also significantly induced Fos in the EWcp neurons. The induction occurred only on the side of the EWcp ipsilateral to the VTA injection. These results indicate that activity of EWcp is inhibited by tonic activity of dopaminergic VTA neurons, and that unilateral projections of VTA onto Ucn1-containing EWcp neurons provide a link between systems regulating approach and avoidance behaviors.

Keywords: Dopamine; Edinger–Westphal nucleus; Stress; Tonic inhibition; Urocortin.

Copyright © 2013 Elsevier B.V. All rights reserved.

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Figures

Figure 1
Figure 1

Representative images showing verification intra-VTA location of cannula tracks (A), Fos immunoreactivity in EWcp following intra-VTA injections of saline (B), Fos immunoreactivity in EWcp following intra-VTA injections of muscimol (C), Fos immunoreactivity in EWcp following intraperitoneal injection of 2.5 g/kg of ethanol (D). Scale bar for panels B–D indicates 100 microns.

Figure 2
Figure 2

Number of Fos-positive neurons of EWcp following either intra-VTA injection of saline (N=7), intra-VTA injection of muscimol (N=14) or intraperitoneal injection of 2.5 g/kg of ethanol (N=3). Fisher PLSD: * - significantly different from all other groups (p<0.05), # - significantly different from Saline (p<0.05).

Figure 3
Figure 3

Number of Fos-positive neurons in the contralateral and ipsilateral side of EWcp following either intra-VTA injection of saline (N=5) or intra-VTA injection of quinpirole (N=8). Fischer PLSD: * - significantly different from all other groups (p<0.05).

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