Abstract:
BACKGROUND:Recent findings indicate that inhibitors of fatty acid amide hydrolase (FAAH) counteract the rewarding effects of nicotine in rats. Inhibition of FAAH increases levels of several endogenous substances in the brain, including the endocannabinoid anandamide and the noncannabinoid fatty acid ethanolamides oleoylethanolamide (OEA) and palmitoylethanolamide, which are ligands for alpha-type peroxisome proliferator-activated nuclear receptors (PPAR-α). Here, we evaluated whether directly acting PPAR-α agonists can modulate reward-related effects of nicotine. METHODS:We combined behavioral, neurochemical, and electrophysiological approaches to evaluate effects of the PPAR-α agonists [[4-Chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]thio]acetic acid (WY14643) and methyl oleoylethanolamide (methOEA; a long-lasting form of OEA) on 1) nicotine self-administration in rats and squirrel monkeys; 2) reinstatement of nicotine-seeking behavior in rats and monkeys; 3) nicotine discrimination in rats; 4) nicotine-induced electrophysiological activity of ventral tegmental area dopamine neurons in anesthetized rats; and 5) nicotine-induced elevation of dopamine levels in the nucleus accumbens shell of freely moving rats. RESULTS:The PPAR-α agonists dose-dependently decreased nicotine self-administration and nicotine-induced reinstatement in rats and monkeys but did not alter food- or cocaine-reinforced operant behavior or the interoceptive effects of nicotine. The PPAR-α agonists also dose-dependently decreased nicotine-induced excitation of dopamine neurons in the ventral tegmental area and nicotine-induced elevations of dopamine levels in the nucleus accumbens shell of rats. The ability of WY14643 and methOEA to counteract the behavioral, electrophysiological, and neurochemical effects of nicotine was reversed by the PPAR-α antagonist 1-[(4-Chlorophenyl)methyl]-3-[(1,1-dimethylethyl)thio]-a,a-dimethyl-5-(1-methylethyl)-1H-Indole-2-propanoic acid (MK886). CONCLUSIONS:These findings indicate that PPAR-α might provide a valuable new target for antismoking medications.
journal_name
Biol Psychiatryjournal_title
Biological psychiatryauthors
Mascia P,Pistis M,Justinova Z,Panlilio LV,Luchicchi A,Lecca S,Scherma M,Fratta W,Fadda P,Barnes C,Redhi GH,Yasar S,Le Foll B,Tanda G,Piomelli D,Goldberg SRdoi
10.1016/j.biopsych.2010.07.009subject
Has Abstractpub_date
2011-04-01 00:00:00pages
633-41issue
7eissn
0006-3223issn
1873-2402pii
S0006-3223(10)00716-Xjournal_volume
69pub_type
杂志文章abstract:BACKGROUND:The interactions among experience, emotion, and memory are considered to be instrumental in the ontogeny and maintenance of acquired emotional and behavioral disorders (e.g., phobias). Here we address the question whether an anxiety-like state can associate with taste to produce conditioned taste aversion (C...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2004.08.024
更新日期:2004-12-01 00:00:00
abstract:BACKGROUND:Neurobiologic abnormalities in the thalamus have been implicated in the pathophysiology of obsessive-compulsive disorder. We recently reported increased thalamic volume in treatment-naive pediatric obsessive-compulsive disorder patients versus case-matched healthy comparison subjects that decreased to levels...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(00)00902-1
更新日期:2000-08-15 00:00:00
abstract:BACKGROUND:Emotional vulnerabilities at the core of borderline personality disorder (BPD) involve a dysfunction of frontolimbic systems subserving negative emotionality. The specific regions identified in individual studies, however, vary widely and provide an incomplete understanding of the functional brain abnormalit...
journal_title:Biological psychiatry
pub_type: 杂志文章,meta分析
doi:10.1016/j.biopsych.2012.07.014
更新日期:2013-01-15 00:00:00
abstract:BACKGROUND:How clozapine exerts superior antipsychotic efficacy in treatment-resistant schizophrenia is not known. Moderate (rather than "full") occupancy of D2 postsynaptic receptors may be crucial, perhaps by achieving a more effective D1/D2 or serotonin-2a/D2 ratio. The objective of this study was to test the modera...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
doi:10.1016/S0006-3223(98)00226-1
更新日期:1998-01-15 00:00:00
abstract::Dietary administration of L-tryptophan to rats failed to increase blood platelets. Instead platelet counts were decreased after feeding either a tryptophan-deficient or tryptophan-enriched (10%) diet, but were unchanged in animals on a 1% tryptophan diet. Platelet median volumes were not affected by any of these dieta...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
更新日期:1980-12-01 00:00:00
abstract::Mood disorders are the leading causes of morbidity and mortality in children and adolescence. As a result, many adolescents are treated with psychopharmacologic agents such as antidepressants and mood stabilizers. To date, research into the safety and efficacy of these medications has lagged behind clinical practice. ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(01)01149-0
更新日期:2001-06-15 00:00:00
abstract:BACKGROUND:Fatigue is highly prevalent and causes serious disruption in quality of life. Although the underlying biological mechanism is unknown, increases in inflammation have been implicated. This prospective study examined the association between C-reactive protein (CRP), a biomarker of systemic inflammation, and fa...
journal_title:Biological psychiatry
pub_type: 杂志文章,多中心研究
doi:10.1016/j.biopsych.2009.06.008
更新日期:2009-11-01 00:00:00
abstract::Psychiatric disorders show high rates of comorbidity and nonspecificity of presenting clinical symptoms, while demonstrating substantial heterogeneity within diagnostic categories. Notably, many of these psychiatric disorders first manifest in youth. We review progress and next steps in efforts to parse heterogeneity ...
journal_title:Biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/j.biopsych.2019.12.015
更新日期:2020-07-01 00:00:00
abstract::EEGs were recorded for two groups of chronic alcoholics who scored at opposite extremes on the Shipley Institute of Living Scale. The groups were matched in terms of age and drinking history variables and were compared to age-matched control subjects for left and right precentral (F-T) and postcentral (C-O) placements...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
更新日期:1978-12-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2005.10.007
更新日期:2006-07-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(92)90116-h
更新日期:1992-05-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(93)90153-5
更新日期:1993-11-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2005.07.011
更新日期:2006-03-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(02)01400-2
更新日期:2002-11-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.biopsych.2013.12.005
更新日期:2014-10-01 00:00:00
abstract::Ten patients with panic disorder and 10 matched control subjects were compared as to their blood pressure and heart rate during regular daily activity. Physiological responses were monitored by ambulatory recorder, and subjective reports of mood were collected. Data were analyzed controlling for activity and stress le...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(95)00048-8
更新日期:1995-11-15 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/j.biopsych.2018.01.014
更新日期:2018-06-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
doi:10.1016/j.biopsych.2005.04.056
更新日期:2005-12-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2004.12.026
更新日期:2005-03-01 00:00:00
abstract::Cannabis use has been reported to increase the risk of developing schizophrenia and to worsen symptoms of the illness. Both of these outcomes might be attributable to the disruption by cannabis of the endogenous cannabinoid system's spatiotemporal regulation of the inhibitory circuitry in the prefrontal cortex that is...
journal_title:Biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/j.biopsych.2015.06.015
更新日期:2016-04-01 00:00:00
abstract::The growth hormone (GH) response to GH-releasing hormone (GHRH) is characteristically exaggerated in anorexia nervosa (AN). Hyperglycemia suppresses the GH response to GHRH in normal subjects. To test whether this inhibitory action of hyperglycemia is preserved in AN, we performed a GHRH (GHRH 1-40, 1 micrograms/kg) t...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(90)90651-h
更新日期:1990-01-15 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2011.05.016
更新日期:2011-11-15 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(97)00546-5
更新日期:1999-02-01 00:00:00
abstract:BACKGROUND:The endocannabinoid anandamide may be involved in the regulation of emotional reactivity. In particular, it has been shown that pharmacological inhibition of the enzyme fatty acid amide hydrolase (FAAH), which catalyzes the intracellular hydrolysis of anandamide, elicits anxiolytic-like and antidepressant-li...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2006.12.001
更新日期:2007-11-15 00:00:00
abstract:BACKGROUND:Disruptions of emotional information processing (i.e., attention to, memory for, and interpretation of emotional information) have been implicated in the onset and maintenance of depression. The research presented here investigated cognitive and psychophysiological features of a particularly promising correl...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(00)01024-6
更新日期:2001-04-01 00:00:00
abstract::Plasma norepinephrine (NE), free 3-methoxy-4-hydroxyphenethylene glycol (MHPG), and binding of tritiated yohimbine to platelet membranes were measured in 14 patients with generalized anxiety disorder (GAD), who were matched for age and sex with 14 patients with unipolar major depressive disorder (MDD) and 14 normal su...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(89)90158-3
更新日期:1989-01-15 00:00:00
abstract::Extensive work in the field has indicated a state-dependent hyperactivity of the hypothalamic-pituitary-adrenocortical (HYPAC) functions and unresponsiveness to dexamethasone suppression in at least 50% of patients suffering from endogenous depression. In this study, elderly outpatients, 60-85 years of age, suffering ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
更新日期:1984-05-01 00:00:00
abstract:BACKGROUND:Problems with the voluntary control of behavior, such as those leading to increased antisaccade errors, are accepted as evidence of prefrontal dysfunction in schizophrenia. We previously reported that speeded prosaccade responses, i.e., shorter response latencies for automatic shifts of attention to visual t...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2007.11.009
更新日期:2008-04-15 00:00:00
abstract::A group of 29 bipolar manic-depressives completed a 12-month double-blind cross-over trial of low-dose and high-dose lithium prophylaxis. Twelve patients relapsed, and significantly more of the relapses occurred during the low-dose 6-month phase of the trial. There was a trend for relapse to occur within 2 months of a...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
更新日期:1982-11-01 00:00:00
abstract:BACKGROUND:Despite widely replicated abnormalities of gamma-aminobutyric acid (GABA) neurons in schizophrenia postmortem, few studies have measured tissue GABA levels in vivo. We used proton magnetic resonance spectroscopy to measure tissue GABA levels in participants with schizophrenia and healthy control subjects in ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2010.05.016
更新日期:2010-10-01 00:00:00