Abstract:
:Acute morphine administration produces analgesia and reward, but prolonged use may lead to analgesic tolerance in patients chronically treated for pain and to compulsive intake in opioid addicts. Moreover, long-term exposure may induce physical dependence, manifested as somatic withdrawal symptoms in the absence of the drug. We set up three behavioral paradigms to model these adaptations in mice, using distinct regimens of repeated morphine injections to induce either analgesic tolerance, locomotor sensitization or physical dependence. Interestingly, mice tolerant to analgesia were not sensitized to hyperlocomotion, whereas sensitized mice displayed some analgesic tolerance. We then examined candidate molecular modifications that could underlie the development of each behavioral adaptation. First, analgesic tolerance was not accompanied by mu opioid receptor desensitization in the periaqueductal gray. Second, cdk5 and p35 protein levels were unchanged in caudate-putamen, nucleus accumbens and prefrontal cortex of mice displaying locomotor sensitization. Finally, naloxone-precipitated morphine withdrawal did not enhance basal or forskolin-stimulated adenylate cyclase activity in nucleus accumbens, prefrontal cortex, amygdala, bed nucleus of stria terminalis or periaqueductal gray. Therefore, the expression of behavioral adaptations to chronic morphine treatment was not associated with the regulation of micro opioid receptor, cdk5 or adenylate cyclase activity in relevant brain areas. Although we cannot exclude that these modifications were not detected under our experimental conditions, another hypothesis is that alternative molecular mechanisms, yet to be discovered, underlie analgesic tolerance, locomotor sensitization and physical dependence induced by chronic morphine administration.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Contet C,Filliol D,Matifas A,Kieffer BLdoi
10.1016/j.neuropharm.2007.10.015subject
Has Abstractpub_date
2008-03-01 00:00:00pages
475-86issue
3eissn
0028-3908issn
1873-7064pii
S0028-3908(07)00346-2journal_volume
54pub_type
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journal_title:Neuropharmacology
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doi:10.1016/s0028-3908(98)00192-0
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journal_title:Neuropharmacology
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pub_type: 杂志文章
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更新日期:2016-10-01 00:00:00
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journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2011.05.008
更新日期:2011-09-01 00:00:00
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journal_title:Neuropharmacology
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更新日期:1998-04-01 00:00:00
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更新日期:2016-10-01 00:00:00
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pub_type: 杂志文章
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journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(88)90059-7
更新日期:1988-10-01 00:00:00
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pub_type: 杂志文章
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更新日期:2000-09-01 00:00:00
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journal_title:Neuropharmacology
pub_type: 杂志文章
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更新日期:2015-10-01 00:00:00
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journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2016.01.014
更新日期:2016-06-01 00:00:00
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journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(83)90026-6
更新日期:1983-09-01 00:00:00
abstract::Dopamine neurons in the ventral tegmental area (VTA) play a very important role in a variety of physiological as well as addictive behaviors. However, a clear understanding of the cellular mechanisms underlying these behaviors is still missing. Within the VTA, recent studies have shown that forms of synaptic plasticit...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2008.07.024
更新日期:2009-01-01 00:00:00
abstract::There is evidence that adenosine is an endogenous neuroprotective substance in the gerbil and that propentofylline, a novel xanthine derivative that acts as a transport inhibitor, exerts part of its neuroprotective activity in this species by enhancing adenosine actions. Using autoradiography we have examined the dist...
journal_title:Neuropharmacology
pub_type: 杂志文章
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更新日期:1996-01-01 00:00:00
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更新日期:2009-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/0028-3908(83)90258-7
更新日期:1983-01-01 00:00:00
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journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2015.02.003
更新日期:2015-06-01 00:00:00
abstract::In nonhuman primates, anxiety levels are typically assessed by observing social hierarchies or behavior in an intruder task. As measures of anxiety might influence performance on a particular cognitive task, it is important to analyze these measures in the same room as used for the cognitive task. As we use a playroom...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2011.08.014
更新日期:2012-01-01 00:00:00