Abstract:
:Family, twin and adoption studies demonstrate clearly that alcohol dependence and alcohol use disorders are phenotypically complex and heritable. The heritability of alcohol use disorders is estimated at approximately 50-60% of the total phenotypic variability. Vulnerability to alcohol use disorders can be due to multiple genetic or environmental factors or their interaction which gives rise to extensive and daunting heterogeneity. This heterogeneity makes it a significant challenge in mapping and identifying the specific genes that influence alcohol use disorders. Genetic linkage and (candidate gene) association studies have been used now for decades to map and characterize genomic loci and genes that underlie the genetic vulnerability to alcohol use disorders. These approaches have been moderately successful in identifying several genes that contribute to the complexity of alcohol use disorders. Recently, genome-wide association studies have become one of the major tools for identifying genes for alcohol use disorders by examining correlations between millions of common single-nucleotide polymorphisms with diagnosis status. Genome-wide association studies are just beginning to uncover novel biology; however, the functional significance of results remains a matter of extensive debate and uncertainty. In this review, we present a select group of genome-wide association studies of alcohol dependence, as one example of a way to generate functional hypotheses, within the addiction cycle framework. This analysis may provide novel directions for validating the functional significance of alcohol dependence candidate genes. This article is part of the Special Issue entitled "Alcoholism".
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Reilly MT,Noronha A,Goldman D,Koob GFdoi
10.1016/j.neuropharm.2017.01.017subject
Has Abstractpub_date
2017-08-01 00:00:00pages
3-21eissn
0028-3908issn
1873-7064pii
S0028-3908(17)30017-5journal_volume
122pub_type
杂志文章,评审abstract::The guinea-pig substantia nigra receives a 5-hydroxytryptaminergic (5-HT ergic) projection from the dorsal raphé nucleus. In this study we have attempted to identify the 5-HT receptor subtype mediating release of acetylcholinesterase (AChE) from nigral neurones, measured by assay of perfusate obtained via chronically ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(95)00088-n
更新日期:1995-09-01 00:00:00
abstract::Fluorescence based probes provide a novel way to study the dynamic internalization process of G protein-coupled receptors (GPCRs). Recent advances in the rational design of fluorescent ligands for GPCRs have been used here to generate new fluorescent agonists containing tripeptide linkers for the adenosine A3 receptor...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2015.04.013
更新日期:2015-11-01 00:00:00
abstract::Dopamine (DA)-replacement therapy utilizing l-DOPA is the gold standard symptomatic treatment for Parkinson's disease (PD). A critical complication of this therapy is the development of l-DOPA-induced dyskinesia (LID). The endogenous opioid peptides, including enkephalins and dynorphin, are co-transmitters of dopamine...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2018.09.005
更新日期:2018-10-01 00:00:00
abstract::Chlorpromazine, given either subcutaneously (0.375 mg/kg) or unilaterally into the preoptic/anterior hypothalamic area through a chronically implanted cannula (20 micrograms), was found to enhance the hypothermic response to delta-9-tetrahydrocannabinol (THC; 5 mg/kg i.p.) in unrestrained adult male MF1 mice, kept at ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(88)90164-5
更新日期:1988-02-01 00:00:00
abstract::To identify the enzymes involved in the induction of N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) at CA1 synapses of two-week-old rats we have tested various kinase inhibitors. Surprisingly, given the large body of evidence supporting a role for calcium/calmodulin-dependent protein kinas...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(03)00336-8
更新日期:2003-11-01 00:00:00
abstract::Intrathecal (IT) injection of neostigmine (a cholinesterase inhibitor) has been reported to produce a significant anti-nociceptive effect in a number of inflammatory pain models. However, a potential anti-inflammatory effect of IT neostigmine in these models has not been investigated. In the present study, we have exa...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2004.12.024
更新日期:2005-09-01 00:00:00
abstract::The group II metabotropic glutamate receptor (mGluR) antagonists LY341495 and LY366457 were profiled for their effects on locomotor activity in mice. Both compounds significantly increased locomotor activity. Observational studies showed that rearing was also selectively increased. LY366457-induced hyperactivity was s...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(03)00232-6
更新日期:2003-10-01 00:00:00
abstract::Although there is evidence from in vitro studies to suggest that NO synthesis may be involved in the induction of hippocampal LTP, other in vitro studies and experiments conducted in vivo have provided conflicting results. In agreement with previous work conducted in this laboratory using an i.p. route of administrati...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(94)90040-x
更新日期:1994-11-01 00:00:00
abstract::The effects of 5-hydroxytryptamine (5-HT) on neuronal excitability, evaluated as depolarization-induced firing rate, and on amino acid release, measured as electrically-evoked [(3)H]GABA and [(3)H]d-aspartate efflux, were investigated in rat primary cortical neuronal cultures. 5-HT displayed a concentration-dependent,...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2006.10.017
更新日期:2007-03-01 00:00:00
abstract::Adinazolam (ADI) is a new benzodiazepine with anxiolytic and antidepressant properties. To assess its effects on the acute stress response, rats were given a single intraperitoneal injection of 2.5 or 5.0 mg/kg of ADI and stressed for 1 hr by restraint. Neither dose of ADI had any effect on heart rate, blood pressure ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(92)90157-k
更新日期:1992-01-01 00:00:00
abstract::The effect of sumatriptan, a selective 5-HT1D receptor agent, on extracellular levels of 5-HT in the frontal cortex of the guinea pig was measured by intracerebral dialysis. A constant infusion of sumatriptan (10(-8)-10(-7) M) dose-dependently reduced extracellular levels of 5-HT (e.g. 80 +/- 2% decrease from control ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(90)90061-u
更新日期:1990-06-01 00:00:00
abstract::Amyotrophic Lateral Sclerosis (ALS) mostly affects motor neurons, but non-motor neural and cognitive alterations have been reported in ALS mouse models and patients. Here, we evaluated if time-dependent biphasic changes in synaptic transmission and plasticity occur in hippocampal synapses of ALS SOD1G93A mice. Recordi...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2020.108106
更新日期:2020-07-01 00:00:00
abstract::Desensitization of the nicotinic acetylcholine receptor (nAChR) containing the β2 subunit is a potentially critical mechanism underlying the body weight (BW) reducing effects of nicotine. The purpose of this study was a) to determine the α subunit(s) that partners with the β2 subunit to form the nAChR subtype that end...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2019.107921
更新日期:2020-04-01 00:00:00
abstract::Data have been collected indicating possible functions for histamine in brain but there are only a very few data, collected exclusively with behavioural tests, about the effects of histamine on the perception of the pain, an important aspect in the homeostasis of the human body. The purpose of the present study was to...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(92)90133-a
更新日期:1992-09-01 00:00:00
abstract::The autoradiographic distribution of binding sites for [3H]AMPA, [3H]kainate, [3H]MK-801 and [3H]L-glutamate and the in situ hybridization of GluR-A, GluR-B, GluR-C and GluR-D in rat spinal cord sections were determined. All of the radioligands had similar localisations with the dorsal horn being the most intensely la...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(93)90127-o
更新日期:1993-01-01 00:00:00
abstract::In urethane-chloralose anesthetized, neuromuscularly blocked, ventilated rats, microinjection of NMDA (12 pmol) into the right fourth thoracic segment (T4) spinal intermediolateral nucleus (IML) immediately increased ipsilateral brown adipose tissue (BAT) sympathetic nerve activity (SNA; peak +492% of control), expire...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2007.10.019
更新日期:2008-03-01 00:00:00
abstract::Activation of 5-HT2C receptors in limbic structures such as the amygdala and hippocampus increases anxiety. Indirect evidence obtained with non-selective 5-HT2C-interacting drugs suggests that the same may occur in the dPAG, a brainstem region consistently implicated in the genesis/regulation of panic attacks. In this...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2010.09.001
更新日期:2011-02-01 00:00:00
abstract::Remifentanil is a powerful mu-opioid (MOP) receptor agonist used in anaesthesia with a very short half-life. However, per-operative perfusion of remifentanil was shown to increase morphine consumption during post-operative period to relieve pain. In the present study, we aimed to describe the cellular mechanisms respo...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2013.06.010
更新日期:2013-10-01 00:00:00
abstract::The surface expression and metabolic turnover time of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors are important factors in determining the involvement of these proteins in synaptic function. We used the membrane-impermeant chemical crosslinking reagent BS3 and subsequent immunoblot analysis t...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(98)00135-x
更新日期:1998-10-01 00:00:00
abstract::Effects of cations on binding of 0.1-10 nM 3H-ADTN to calf caudate membranes included decreased apparent Bmax by [Na+] greater than or equal to 100 mM, little effect on Kd or on affinity of other dopamine (DA) agonists (DA and apomorphine), decreased slopes of inhibition curves produced by agonists, but increased affi...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(87)90159-6
更新日期:1987-06-01 00:00:00
abstract::Recent studies indicated that epigenetic modification, especially DNA methylation, play an important role in the persistence of addiction-related memory. 5-aza-2-deoxycytidine (5-aza), an inhibitor of DNA methyltransferases, was approved for clinical treatment. However, it is not clear whether 5-aza is involved in opi...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2014.08.005
更新日期:2014-11-01 00:00:00
abstract::In rodents, insufficient adenosine produces behavioral and physiological symptoms consistent with several comorbidities of autism. In rodents and humans, stimuli postulated to increase adenosine can ameliorate these comorbidities. Because adenosine is a broad homeostatic regulator of cell function and nervous system a...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2012.08.013
更新日期:2013-05-01 00:00:00
abstract::Conantokin-G (con-G), conantokin-T (con-T), a truncated conantokin-R (con-R[1-17]), that functions the same as wild-type con-R, and variant sequences of con-T, were chemically synthesized and employed to investigate their selectivities as antagonists of glutamate/glycine-evoked ion currents in human embryonic kidney-2...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2007.04.016
更新日期:2007-07-01 00:00:00
abstract::1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), or 0.9% saline, was administered to a group of common marmosets initially treated with the toxin 12-18 months previously. Initial treatment had consisted of a cumulative dose of 6-22 mg/kg (i.p.) which caused marked parkinsonism. Subsequently, the animals gradually ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(89)90122-6
更新日期:1989-10-01 00:00:00
abstract::We have examined the effects of a variety of classical and atypical neuroleptic drugs on mitochondrial NADH ubiquinone oxido-reductase (complex I) activity. Sagittal slices of mouse brain incubated in vitro with haloperidol (10 nM) showed time- and concentration-dependent inhibition of complex I. Similar concentration...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(98)00215-9
更新日期:1999-04-01 00:00:00
abstract::Anxiety and depression are considered as stress-related disorders, which present considerable sex differentiation. In animal models of anxiety and depression sex differences have been described and linked to the sexually dimorphic hypothalamus-pituitary-adrenals (HPA) axis. The present study aimed to adjust corticoste...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2011.08.025
更新日期:2012-01-01 00:00:00
abstract::Endocannabinoids are suggested to control pain, even though their clinical use is not fully validated and the underlying mechanisms are incompletely understood. To clarify the targets of endocannabinoid actions, we studied how activation of the endocannabinoid CB1 receptor (CB1R) affects neuronal responses in two in v...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2017.12.013
更新日期:2018-03-15 00:00:00
abstract::Extracellular brain pH fluctuates in both physiological and disease conditions. The main postsynaptic proton receptor is the acid-sensing ion channels (ASICs). During the past decade, much progress has been made on protons, ASICs, and neurological disease. This review summarizes the recent progress on synaptic role of...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2014.12.010
更新日期:2015-07-01 00:00:00
abstract::Physical exercise has become a potentially beneficial therapy for reducing neurodegeneration symptoms in Alzheimer's disease. Previous studies have shown that cognitive deterioration, anxiety and the startle response observed in 7-month-old 3xTg-AD mice were ameliorated after 6 months of free access to a running wheel...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2014.01.037
更新日期:2014-06-01 00:00:00
abstract::The effects of d-amphetamine (0.03-10.0 mg/kg), caffeine (0.3-100.0 mg/kg), nicotine (0.003-10.0 mg/kg) and cocaine (0.03-56.0 mg/kg) were compared on responding maintained under three different schedules of food presentation in mice. Cumulative doses of d-amphetamine, nicotine and cocaine only decreased responding ma...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(86)90160-7
更新日期:1986-10-01 00:00:00