Linked Life Data

14602811

Source:http://linkedlifedata.com/resource/pubmed/id/14602811

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
31
pubmed:dateCreated
2003-11-6
pubmed:abstractText
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 micro-opioid receptor (MOR). In contrast, kappa-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 microm) 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 nm). 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-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin) (3 microm) 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
5
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9981-6
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:14602811-Analgesics, pubmed-meshheading:14602811-Animals, pubmed-meshheading:14602811-Benzeneacetamides, pubmed-meshheading:14602811-Dopamine, pubmed-meshheading:14602811-Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, pubmed-meshheading:14602811-Male, pubmed-meshheading:14602811-Mesencephalon, pubmed-meshheading:14602811-Naltrexone, pubmed-meshheading:14602811-Narcotic Antagonists, pubmed-meshheading:14602811-Neural Inhibition, pubmed-meshheading:14602811-Neurons, pubmed-meshheading:14602811-Patch-Clamp Techniques, pubmed-meshheading:14602811-Pyrrolidines, pubmed-meshheading:14602811-Rats, pubmed-meshheading:14602811-Rats, Sprague-Dawley, pubmed-meshheading:14602811-Receptors, Opioid, kappa, pubmed-meshheading:14602811-Receptors, Opioid, mu, pubmed-meshheading:14602811-Ventral Tegmental Area
pubmed:year
2003
pubmed:articleTitle
Kappa-opioid agonists directly inhibit midbrain dopaminergic neurons.
pubmed:affiliation
Joint University of California San Francisco/University of California, Berkeley Bioengineering Graduate Group, San Francisco, California 94143-0775, USA. emargoli@socrates.berkeley.edu
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't