Linked Life Data

18831991

Source:http://linkedlifedata.com/resource/pubmed/id/18831991

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-12-22
pubmed:abstractText
Classically, it has been thought that high-affinity nicotinic receptors-containing beta2 subunits are the most important receptor subtypes for nicotinic involvement in cognitive function and nicotine self-administration, while low affinity alpha7-containing nicotinic receptors have not been thought to be important. In the current study, we found that knockout of either beta2 or alpha7 subunits caused significant deficits in spatial discrimination in mice. The character of the impairment in the two knockouts was different. The beta2 knockout preferentially impaired cognition in males while the alpha7 caused impairment regardless of sex. Both beta2- and alpha7-containing nicotinic receptors also are important for nicotine self-administration, also in different ways. Most animal model studies of nicotine self-administration are relatively short-term whereas the problem of tobacco addiction is considerably longer-term. To better model the impact of nicotinic receptor subtypes on nicotine self-administration over the long-term, we studied the impact of genetic knockout of low affinity alpha7 receptors vs. high-affinity beta2-containing nicotinic receptors. Mice with knockouts of either of these receptors and their wildtype counter parts were given free access to a choice of nicotine-containing and nicotine-free solution in their home cages on a continuous basis over a period of 5 months. During the first few weeks, the beta2-containing nicotinic receptor knockout mice showed a significant decrease in nicotine consumption relative to wildtype mice, whereas the alpha7 knockout mice did not significantly differ from wildtype controls at the beginning of their access to nicotine. Interestingly, in the longer-term after the first few weeks of nicotine access, the beta2 knockout mice returned to wildtype mouse levels of nicotine consumption, whereas the alpha7 knockout mice developed an emergent decrease in nicotine consumption. The alpha7 receptor knockout-induced decrease in nicotine consumption persisted for the 5-month period of the study. Both alpha7- and beta2-containing nicotinic receptors play critical roles in cognitive function and nicotine self-administration. Regarding cognitive function, beta2-containing receptors are important for maintaining normal sex differences in spatial learning and memory, whereas alpha7 receptors are important for cognitive function regardless of sex. Regarding nicotine self-administration high-affinity beta2-containing nicotinic receptors are important for consumption during the initial phase of nicotine access, but it is the alpha7 nicotinic receptors that are important for the longer-term regulation of nicotine consumption.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-10454356, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-10460318, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-10780509, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-11044746, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-11834293, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-11875631, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-11927157, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-11955523, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-13679247, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-14975691, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-15489024, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-16133126, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-16220335, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-16556437, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-16650968, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-16826402, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-17019565, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-17061109, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-17115136, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-17308038, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-17898229, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-17913920, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-18034231, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-18265960, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-9428762, http://linkedlifedata.com/resource/pubmed/commentcorrection/18831991-9651527
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1872-7549
pubmed:author
pubmed:issnType
Electronic
pubmed:day
23
pubmed:volume
196
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
207-13
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Nicotinic alpha7- or beta2-containing receptor knockout: effects on radial-arm maze learning and long-term nicotine consumption in mice.
pubmed:affiliation
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA. edlevin@duke.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural