In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 23, No. 31 ( 2003-11-05), p. 9981-9986
Abstract:
Dopaminergic neurons of the ventral tegmental area (VTA) play a critical role in motivation and reinforcement of goal-directed behaviors. Furthermore, excitation of these neurons has been implicated in the addictive process initiated by drugs such as morphine that act at the μ-opioid receptor (MOR). In contrast, κ-opioid receptor (KOR) activation in the VTA produces behavioral actions opposite to those elicited by MOR activation. The mechanism underlying this functional opposition, however, is poorly understood. VTA neurons have been categorized previously as principal, secondary, or tertiary on the basis of electrophysiological and pharmacological characteristics. In the present study using whole-cell patch-clamp recordings, we demonstrate that a selective KOR agonist (U69593, 1 μ m ) directly inhibits a subset of principal and tertiary but not secondary neurons in the VTA. This KOR-mediated inhibition occurs via the activation of a G-protein-coupled inwardly rectifying potassium channel and is blocked by the selective KOR antagonist nor-Binaltorphimine (100 n m ). Significantly, regardless of cell class, KOR-mediated inhibition was found only in tyrosine hydroxylase-immunoreactive and thus dopaminergic neurons. In addition, we found a subset of principal neurons that exhibited both disinhibition by a selective MOR agonist ([ d -Ala 2 , N -Me-Phe 4 , Gly-ol 5 ]-enkephalin) (3 μ m ) and direct inhibition by KOR agonists. These results provide a cellular mechanism for the opposing behavioral effects of KOR and MOR agonists and shed light on how KORs might regulate the motivational effects of both natural rewards and addictive drugs.
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.23-31-09981.2003
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
2003
detail.hit.zdb_id:
1475274-8
SSG:
12
