Abstract:
:Behavioral sensitization to cocaine is associated to neuroadaptations that contribute to addiction. Enkephalin is highly expressed in mesocorticolimbic areas associated with cocaine-induced sensitization; however, their influence on cocaine-dependent behavioral and neuronal plasticity has not been explained. In this study, we employed a knockout (KO) model to investigate the contribution of enkephalin in cocaine-induced behavioral sensitization. Wild-type (WT) and proenkephalin KO mice were treated with cocaine once daily for 9 days to induce sensitization. Additionally, to clarify the observations in KO mice, the same procedure was applied in C57BL/6 mice, except that naloxone was administered before each cocaine injection. All animals received a cocaine challenge on days 15 and 21 of the treatment to evaluate the expression of locomotor sensitization. On day 21, microdialysis measures of accumbal extracellular dopamine, Western blotting for GluR1 AMPA receptor (AMPAR), phosphorylated ERK2 (pERK2), CREB (pCREB), TrKB (pTrkB) were performed in brain areas relevant for sensitization from KO and WT and/or naloxone- and vehicle pre-treated animals. We found that KO mice do not develop sensitization to the stimulating properties of cocaine on locomotor activity and on dopamine release in the nucleus accumbens (NAc). Furthermore, pivotal neuroadaptations such as the increase in pTrkB receptor, pERK/CREB and AMPAR related to sensitized responses were absent in the NAc from KO mice. Consistently, full abrogation of cocaine-induced behavioral and neuronal plasticity after naloxone pre-treatment was observed. We show for first time that the proenkephalin system is essential in regulating long-lasting pivotal neuroadaptations in the NAc underlying behavioral sensitization to cocaine.
journal_name
Addict Bioljournal_title
Addiction biologyauthors
Mongi-Bragato B,Zamponi E,García-Keller C,Assis MA,Virgolini MB,Mascó DH,Zimmer A,Cancela LMdoi
10.1111/adb.12200subject
Has Abstractpub_date
2016-03-01 00:00:00pages
326-38issue
2eissn
1355-6215issn
1369-1600journal_volume
21pub_type
杂志文章abstract::Phosphatidylethanol (PEth), a direct ethanol metabolite, is detectable in blood for more than 2 weeks after sustained ethanol intake. Our aim was to assess the usefulness of PEth [comparing sensitivity, specificity and the area under the curve (AUC)] as compared with carbohydrate-deficient transferrin (CDT), gamma-glu...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1111/j.1369-1600.2006.00040.x
更新日期:2007-03-01 00:00:00
abstract::Chronic exposure to alcohol and other drugs of abuse has been associated with deleterious consequences, including functional connectivity deficits within neural networks associated with executive control. Altered functional connectivity within the executive control network (ECN) might underlie the progressive inabilit...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1111/adb.12684
更新日期:2020-01-01 00:00:00
abstract::Although our previous studies have demonstrated both protein kinase C (PKC) and GluN2B-containing N-methyl-d-aspartate receptor (GluN2B-NMDAR) play crucial roles in morphine-associated learning and memory, the relationship between them remains unexplored. In this study, we validated the enhanced PKC and membrane GluN2...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1111/adb.12558
更新日期:2018-09-01 00:00:00
abstract::Recreational use of the drug 4-methylmethcathinone (mephedrone; 4-MMC) became increasingly popular in the United Kingdom in recent years, spurred in part by the fact that it was not criminalized until April 2010. Although several fatalities have been associated with consumption of 4-MMC and cautions for recreational u...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1111/adb.12038
更新日期:2013-09-01 00:00:00
abstract::Because of its primary role in drug-seeking, consumption and addictive behaviour, there is a growing interest in identifying the neural circuits and molecular mechanisms underlying the formation, maintenance and retrieval of drug-related memories. Human studies, which focused on neuronal systems that store and control...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1111/adb.12042
更新日期:2014-01-01 00:00:00
abstract::Nicotine dependence (ND) is a chronic disease with catastrophic effects on individual and public health. The glutamate receptor subunit gene, ionotropic N-methyl-d-aspartate 3A (GRIN3A), encodes a crucial subunit of N-methyl-d-aspartate receptors (NMDARs), which play an essential role in synaptic plasticity in the bra...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1111/adb.12718
更新日期:2020-01-01 00:00:00
abstract::Smoking withdrawal is associated with significant deficits in the ability to initiate and maintain attention for extended periods of time (i.e. sustained attention; SA). However, the effects of smoking abstinence on the temporal dynamics of neurocognition during SA have not been evaluated. Twenty adult smokers underwe...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1111/j.1369-1600.2010.00252.x
更新日期:2010-10-01 00:00:00
abstract::Animal and cross-sectional human studies suggest that chronic cocaine use is associated with altered responsivity of the hypothalamic-pituitary-adrenal axis to stress. Moreover, increased susceptibility to stress has been proposed as an important factor for development, maintenance and relapse of cocaine addiction. As...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1111/adb.12632
更新日期:2019-07-01 00:00:00
abstract::The World Health Organization estimates a 12-month prevalence rate of 8+% for an alcohol use disorder (AUD) diagnosis in people age 15 years and older in the United States and Europe, presenting significant health risks that have the potential of accelerating age-related functional decline. According to neuropathologi...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1111/adb.12746
更新日期:2020-05-01 00:00:00
abstract::The effectiveness of using amphetamine isomer ratios to determine individual compliance with a Dexedrine (dexamphetamine, Celltech, Slough, UK) treatment regimen for the maintenance and detoxification from amphetamine abuse has been audited. The calculation of l/d-amphetamine isomer ratios in urine has been shown prev...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1080/13556210310001646411
更新日期:2003-12-01 00:00:00
abstract::Although substantial research effort has focused on developing pharmacological treatments for cocaine abuse, no effective medications have been developed. Recent studies show that enzymes that metabolize cocaine in the periphery, forestalling its entry into the brain, can prevent cocaine toxicity and its behavioral ef...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1111/j.1369-1600.2011.00424.x
更新日期:2013-01-01 00:00:00
abstract::The total concentration of THC has been monitored in cannabis preparations sold in Dutch coffee shops since 1999. This annual monitoring was issued by the Ministry of Health after reports of increased potency. The level of the main psychoactive compound, Delta9-tetrahydrocannabinol (THC), is measured in marijuana and ...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1080/13556210500123217
更新日期:2005-06-01 00:00:00
abstract::The striatum, a major central nervous system structure modulating movement, is enriched with glutamatergic and dopaminergic innervation. By altering activities of both glutamatergic and dopaminergic transmissions the psychostimulants, amphetamine and cocaine, induce behavioral changes in experimental animals. Activati...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1080/13556219971641
更新日期:1999-04-01 00:00:00
abstract::Methamphetamine (METH) is an increasing popular and highly addictive stimulant associated with autonomic nervous system (ANS) dysfunction, cardiovascular pathology and neurotoxicity. Heart rate variability (HRV) has been used to assess autonomic function and predict mortality in cardiac disorders and drug intoxication...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1111/j.1369-1600.2010.00270.x
更新日期:2012-05-01 00:00:00
abstract::Nicotine self-administration is associated with decreased expression of the glial glutamate transporter (GLT-1) and the cystine-glutamate exchange protein xCT within the nucleus accumbens core (NAcore). N-acetylcysteine (NAC) has been shown to restore these proteins in a rodent model of drug addiction and relapse. How...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1111/adb.12797
更新日期:2020-09-01 00:00:00
abstract::The administration of cannabidiol has shown promising evidence in the treatment of some neuropsychiatric disorders, including cocaine addiction. However, little information is available as to the mechanisms by which cannabidiol reduces drug use and compulsive seeking. We investigated the role of adult hippocampal neur...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1111/adb.12778
更新日期:2020-07-01 00:00:00
abstract::Erythroycte delta aminolevulinic acid dehydratase (ALAD) has been suggested as a marker for detecting recent alcohol intake. Unlike other markers, ALAD activity decreases after alcohol intake. Review of the literature suggests that the main interest in this marker is because it increases rapidly after withdrawal. The ...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1080/13556219772778
更新日期:1997-04-01 00:00:00
abstract::Brain-derived neurotrophic factor (BDNF) regulates a variety of physiological processes, and several studies have explored the role of BDNF in addiction-related brain regions like the nucleus accumbens core (NAcore). We sought to understand the rapid effects of endogenous BDNF on cocaine seeking. Rats were trained to ...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1111/adb.12638
更新日期:2019-09-01 00:00:00
abstract::Despite the fact that several data have supported the involvement of the cerebellum in the functional alterations observed after prolonged cocaine use, this brain structure has been traditionally ignored and excluded from the circuitry affected by addictive drugs. In the present study, we investigated the effects of a...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1111/adb.12223
更新日期:2015-09-01 00:00:00
abstract::The controversy over the relationship between heroin addiction and hepatocellular dysfunction was examined by assay of serum activities of aspartate and alanine aminotransferases, total protein, albumin and globulin in 48 chronic heroin smokers and 33 controls. Biliary secretion in the addicts was compared to controls...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1080/1355621961000124826
更新日期:1996-01-01 00:00:00
abstract::Previous studies on acetaldehyde dehydrogenase 2 (ALDH2) focused on drinking behavior or alcoholism because the ALDH2*2 allele protects against the risk of developing alcoholism. The mechanism provides that the ALDH2 gene's protective effect is also involved in dopamine metabolism. The interaction of the ALDH2 gene wi...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1111/j.1369-1600.2010.00268.x
更新日期:2012-09-01 00:00:00
abstract::Following recent advances in neuromodulation therapy for mental disorders, we treated one patient with severe alcohol addiction with deep brain stimulation (DBS) of the nucleus accumbens (NAc). Before and one year following the surgery, we assessed the effects of DBS within the NAc on the addiction as well as on psych...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1111/j.1369-1600.2011.00337.x
更新日期:2011-10-01 00:00:00
abstract::In our society every second polytraumatized patient is a chronic alcoholic. A patient's alcohol-related history is often unavailable and laboratory markers are not sensitive or specific enough to detect alcohol-dependent patients who are at risk of developing alcohol withdrawal syndrome (AWS) during their post-traumat...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1080/1355621961000124726
更新日期:1996-01-01 00:00:00
abstract::Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is the major psychoactive alkaloid of some species of mushrooms distributed worldwide. These mushrooms represent a growing problem regarding hallucinogenic drug abuse. Despite its experimental medical use in the 1960s, only very few pharmacological data about psilocy...
journal_title:Addiction biology
pub_type: 杂志文章,评审
doi:10.1080/1355621021000005937
更新日期:2002-10-01 00:00:00
abstract::The genetic and environmental contributions to differences in response to ethanol have been examined widely using inbred strains, selected lines and genetically engineered (transgenic and 'knock-out') animals. In addition, recombinant inbred strains have been used to identify QTLs (chromosomal regions) associated with...
journal_title:Addiction biology
pub_type: 杂志文章,评审
doi:10.1080/13556210412331308985
更新日期:2005-03-01 00:00:00
abstract::Little is known about the neural functioning that underpins drug valuation and choice in addiction, including nicotine dependence. Following ad libitum smoking, 19 dependent smokers (smoked≥10/day) and 19 occasional smokers (smoked 0.5-5/week) completed a decision-making task. First, participants stated how much they ...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1111/adb.12802
更新日期:2020-07-01 00:00:00
abstract::Through incentive learning, the emotional experience of a reward in a relevant need state (e.g. hunger for food) sets the incentive value that guides the performance of actions that earn that reward when the need state is encountered again. Opiate withdrawal has been proposed as a need state in which, through experien...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1111/adb.12172
更新日期:2016-03-01 00:00:00
abstract::Animal research supports a central role for corticotropin-releasing factor (CRF) in actions of ethanol on brain function. An examination of alcohol consumption in adolescents reported a significant genotype x environment (G x E) interaction involving rs1876831, a corticotropin-releasing hormone receptor 1 (CRHR1) poly...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1111/j.1369-1600.2009.00181.x
更新日期:2010-01-01 00:00:00
abstract::Cigarette smoking is a severe health burden being related to a number of chronic diseases. Frequently, smokers report about sleep problems. Sleep disturbance, in turn, has been demonstrated to be involved in the pathophysiology of several disorders related to smoking and may be relevant for the pathophysiology of nico...
journal_title:Addiction biology
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1369-1600.2012.00487.x
更新日期:2014-05-01 00:00:00
abstract::Ketamine, a non-competitive N-methyl-D-aspartic acid receptor antagonist, has emerged as an increasingly popular drug among young drug abusers worldwide. Available evidence suggests that ketamine produces acute impairments of working, episodic and semantic memory along with psychotogenic and dissociative effects when ...
journal_title:Addiction biology
pub_type: 杂志文章
doi:10.1111/adb.12004
更新日期:2014-03-01 00:00:00