In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 35, No. 8 ( 2015-02-25), p. 3460-3469
Abstract:
The lateral habenula (LHb) is involved in reward and aversion and is reciprocally connected with dopamine (DA)-containing brain regions, including the ventral tegmental area (VTA). We used a multidisciplinary approach to examine the properties of DA afferents to the LHb in the rat. We find that 〉 90% of VTA tyrosine hydroxylase (TH) neurons projecting to the LHb lack vesicular monoamine transporter 2 (VMAT2) mRNA, and there is little coexpression of TH and VMAT2 protein in this mesohabenular pathway. Consistent with this, electrical stimulation of LHb did not evoke DA-like signals, assessed with fast-scan cyclic voltammetry. However, electrophysiological currents that were inhibited by L741,742, a DA-D 4 -receptor antagonist, were observed in LHb neurons when DA uptake or degradation was blocked. To prevent DA activation of D 4 receptors, we repeated this experiment in LHb slices from DA-depleted rats. However, this did not disrupt D 4 receptor activation initiated by the dopamine transporter inhibitor, GBR12935. As the LHb is also targeted by noradrenergic afferents, we examined whether GBR12935 activation of DA-D 4 receptors occurred in slices depleted of norepinephrine (NE). Unlike DA, NE depletion prevented the activation of DA-D 4 receptors. Moreover, direct application of NE elicited currents in LHb neurons that were blocked by L741,742, and GBR12935 was found to be a more effective blocker of NE uptake than the NE-selective transport inhibitor nisoxetine. These findings demonstrate that NE is released in the rat LHb under basal conditions and that it activates DA-D 4 receptors. Therefore, NE may be an important regulator of LHb function.
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.4525-13.2015
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
2015
detail.hit.zdb_id:
1475274-8
SSG:
12
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