Disrupted Ventromedial Prefrontal Function, Alcohol Craving, and Subsequent Relapse Risk

Seo, Dongju; Lacadie, Cheryl; Tuit, Keri; Hong, Kwangik; Constable, R. Todd; Sinha, Rajita

doi:10.1001/jamapsychiatry.2013.762

Cited by 248 publications

(252 citation statements)

References 66 publications

Supporting

Mentioning

235

Contrasting

Unclassified

Order By: Relevance

“…Human-imaging studies suggest that exaggerated activity within select frontal sites, including ventromedial aspects of PFC and anterior cingulate cortex (ACC) (areas roughly homologous to the site studied here), contributes to inhibitory-control deficits in a variety of psychiatric disorders characterized by dysregulated appetitive motivation (Karhunen et al, 2000;Schienle et al, 2009;Seo et al, 2013;Uher et al, 2004) . The present results join a growing number of studies, indicating that these cortical sites represent crucial loci of clinically relevant opioid action.…”

Section: Discussionmentioning

confidence: 78%

“…However, considerable evidence implicates functional abnormalities in frontal cortical sites that are engaged by reward-associated cues and that modulate impulsive reward-seeking behavior (Lock et al, 2011;Schienle et al, 2009). Accordingly, human neuroimaging studies have revealed aberrant frontal activity in drug and behavioral addictions, and in eating disorders (Seo et al, 2013;Uher et al, 2004;Volkow et al, 2005). Neuropsychological assessments in individuals with these disorders have shown deficits in frontally mediated processes such as impulse control and decision-making (Lock et al, 2011;Robbins et al, 2012;Schag et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Endogenous Opioid Signaling in the Medial Prefrontal Cortex is Required for the Expression of Hunger-Induced Impulsive Action

Selleck

Lake

Estrada

et al. 2015

Neuropsychopharmacol

View full text Add to dashboard Cite

Opioid transmission and dysregulated prefrontal cortex (PFC) activity have both been implicated in the inhibitory-control deficits associated with addiction and binge-type eating disorders. What remains unknown, however, is whether endogenous opioid transmission within the PFC modulates inhibitory control. Here, we compared intra-PFC opioid manipulations with a monoamine manipulation (d-amphetamine), in two sucrose-reinforced tasks: progressive ratio (PR), which assays the motivational value of an incentive, and differential reinforcement of low response rates (DRLs), a test of inhibitory control. Intra-PFC methylnaloxonium (M-NX, a limited diffusion opioid antagonist) was given to rats in a 'low-drive' condition (2-h food deprivation), and also after a motivational shift to a 'highdrive' condition (18-h food deprivation). Intra-PFC DAMGO (D-[Ala2,N-MePhe4, Gly-ol]-enkephalin; a μ-opioid agonist) and damphetamine were also tested in both tasks, under the low-drive condition. Intra-PFC M-NX nearly eliminated impulsive action in DRL engendered by hunger, at a dose (1 μg) that significantly affected neither hunger-induced PR enhancement nor hyperactivity. At a higher dose (3 μg), M-NX eliminated impulsive action and returned PR breakpoint to low-drive levels. Conversely, intra-PFC DAMGO engendered 'high-drive-like' effects: enhancement of PR and impairment of DRL performance. Intra-PFC d-amphetamine failed to produce effects in either task. These results establish that endogenous PFC opioid transmission is both necessary and sufficient for the expression of impulsive action in a high-arousal, high-drive appetitive state, and that PFC-based opioid systems enact functionally unique effects on food impulsivity and motivation relative to PFC-based monoamine systems. Opioid antagonists may represent effective treatments for a range of psychiatric disorders with impulsivity features.

show abstract

Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Endogenous Opioid Signaling in the Medial Prefrontal Cortex is Required for the Expression of Hunger-Induced Impulsive Action

Selleck

Lake

Estrada

et al. 2015

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…Although there is enthusiasm for behavioral pharmacology approaches to screen for medications for addiction (Litten et al, 2012;Mason and Higley, 2013;Ray et al, 2010), a required step consists of demonstrating that laboratory-based measures of cue-induced craving and subjective effects do in fact predict treatment response. Notably, recent studies have demonstrated that cue-induced craving predicted relapse among alcohol- (Seo et al, 2013) and heroin- (Fatseas et al, 2011) dependent patients, respectively. Although the present study does not effectively link biobehavioral responses in the laboratory to clinical outcomes, it suggests that NTX reduces cue-induced craving for MA as well as craving and stimulation ratings during MA administration.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Naltrexone on Subjective Response to Methamphetamine in a Clinical Sample: a Double-Blind, Placebo-Controlled Laboratory Study

Ray

Bujarski

Courtney

et al. 2015

Neuropsychopharmacol

View full text Add to dashboard Cite

Methamphetamine (MA) use disorder is a serious psychiatric condition for which there are no FDA-approved medications. Naltrexone (NTX) is an opioid receptor antagonist with demonstrated efficacy, albeit moderate, for the treatment of alcoholism and opioid dependence. Preclinical and clinical studies suggest that NTX may be useful for the treatment of MA use disorder. To inform treatment development, we conducted a double-blind, randomized, crossover, placebo-controlled human laboratory study of NTX. Non-treatmentseeking individuals meeting DSM-IV criteria for MA abuse or dependence (n = 30) completed two separate 5-day inpatient stays. During each admission, participants completed testing sessions comprised of MA cue-reactivity and intravenous MA administration (30 mg) after receiving oral NTX (50 mg) or placebo for 4 days. This study tested the hypotheses that NTX would (a) attenuate cue-induced MA craving, and (b) reduce subjective responses to MA administration. Results largely supported the study hypotheses such that (a) NTX significantly blunted cue-induced craving for MA and (b) attenuated several of the hedonic subjective effects of MA, including craving, during controlled MA administration and as compared with placebo. NTX decreased overall subjective ratings of 'crave drug,' 'stimulated,' and 'would like drug access,' decreased the the post-MA administration timecourse of 'anxious' and increased ratings of 'bad drug effects,' as compared with placebo. These findings support a potential mechanism of action by showing that NTX reduced cue-induced craving and subjective responses to MA. This is consistent with positive treatment studies of NTX for amphetamine dependence, as well as ongoing clinical trials for MA.

show abstract

“…Human neuroimaging evidence suggests that the VmPFC is a key region of the adaptive behavioral coping circuit that plays a role in increased persistence responses in the face of uncontrollable setbacks (21) and in regulation of anxious emotion (22). Disrupted VmPFC signaling during stress also predicts alcohol relapse and failed recovery from alcoholism (23). Childhood trauma, cumulative adversity, and a history of mood disorders or posttraumatic stress disorder (PTSD) are each associated with blunted VmPFC activation during emotion or stress exposure, and disrupted VmPFC connectivity with amygdala is suggestive of poor adaptive coping (13,14,16,24,25).…”

Section: Significancementioning

confidence: 99%

Dynamic neural activity during stress signals resilient coping

Sinha

Lacadie

Constable

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

179

164

View full text Add to dashboard Cite

Active coping underlies a healthy stress response, but neural processes supporting such resilient coping are not well-known. Using a brief, sustained exposure paradigm contrasting highly stressful, threatening, and violent stimuli versus nonaversive neutral visual stimuli in a functional magnetic resonance imaging (fMRI) study, we show significant subjective, physiologic, and endocrine increases and temporally related dynamically distinct patterns of neural activation in brain circuits underlying the stress response. First, stressspecific sustained increases in the amygdala, striatum, hypothalamus, midbrain, right insula, and right dorsolateral prefrontal cortex (DLPFC) regions supported the stress processing and reactivity circuit. Second, dynamic neural activation during stress versus neutral runs, showing early increases followed by later reduced activation in the ventrolateral prefrontal cortex (VLPFC), dorsal anterior cingulate cortex (dACC), left DLPFC, hippocampus, and left insula, suggested a stress adaptation response network. Finally, dynamic stress-specific mobilization of the ventromedial prefrontal cortex (VmPFC), marked by initial hypoactivity followed by increased VmPFC activation, pointed to the VmPFC as a key locus of the emotional and behavioral control network. Consistent with this finding, greater neural flexibility signals in the VmPFC during stress correlated with active coping ratings whereas lower dynamic activity in the VmPFC also predicted a higher level of maladaptive coping behaviors in real life, including binge alcohol intake, emotional eating, and frequency of arguments and fights. These findings demonstrate acute functional neuroplasticity during stress, with distinct and separable brain networks that underlie critical components of the stress response, and a specific role for VmPFC neuroflexibility in stress-resilient coping.functional neuroimaging | stress | resilience coping | binge alcohol intake | emotional eating

show abstract

Disrupted Ventromedial Prefrontal Function, Alcohol Craving, and Subsequent Relapse Risk

Cited by 248 publications

References 66 publications

Endogenous Opioid Signaling in the Medial Prefrontal Cortex is Required for the Expression of Hunger-Induced Impulsive Action

Endogenous Opioid Signaling in the Medial Prefrontal Cortex is Required for the Expression of Hunger-Induced Impulsive Action

The Effects of Naltrexone on Subjective Response to Methamphetamine in a Clinical Sample: a Double-Blind, Placebo-Controlled Laboratory Study

Dynamic neural activity during stress signals resilient coping

Contact Info

Product

Resources

About