Plasma concentrations of β-endorphin, adrenocorticotropic hormone, and cortisol in drinking and abstinent chronic alcoholics

Arbol, J.L. Del; Aguirre, J.C.; Raya, Julio; Rico, Juan José Ruiz; Ruiz-Requena, María Estrella; Miranda, Marı́a Isabel

doi:10.1016/0741-8329(95)00038-0

Cited by 31 publications

(13 citation statements)

References 37 publications

(38 reference statements)

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“…These data, adding to a body of both clinical and basic evidence (cf. del Arbol et al, 1995; Thiagarajan, Mefford, & Eskay, 1989), support the idea that β-endorphin modulates endocrine and behavioral components of the stress response and may contribute to an increased susceptibility for heavy drinking. Moreover, the use of low-endorphin heterozygous mice (βE-HT) in our study enables a more nuanced analysis for the role of this peptide beyond what has been shown in earlier studies only comparing knockouts and wild-types (Mogil et al, 2000; Racz et al, 2008) and may better model the human condition.…”

Section: Discussionsupporting

confidence: 59%

β-endorphin regulates alcohol consumption induced by exercise restriction in female mice

McGonigle

Nentwig

Wilson

et al. 2016

Alcohol

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Animal models have long been used to study the mechanisms underlying the complex association between alcohol and stress. Female mice prevented from running on a home-cage activity wheel increase voluntary ethanol consumption. β-endorphin is an endogenous opioid involved in negatively regulating the stress response and has also been implicated in the risk for excessive drinking. The present study investigates the role of β-endorphin in moderating free-choice consumption of ethanol in response to a blocked activity wheel. Female, transgenic mice with varying levels of the opioid peptide were given daily 2-h access to 20% ethanol with rotations on a running wheel blocked on alternate days. Subjects with low β-endorphin exhibited enhanced stress sensitivity by self-administering larger quantities of ethanol on days when wheel running was prevented. β-endorphin levels did not influence voluntary activity on the running wheel. There were genotypic differences in plasma corticosterone levels as well as corticotropin-releasing hormone mRNA content in multiple brain regions associated with the stress response in these free drinking and running subjects. Susceptibility to stress is enhanced in female mice with low levels of β-endorphin, and better understanding of the role for this opioid in mitigating the response to stressors may aid in the development of interventions and treatments for excessive use of alcohol in women.

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Section: Discussionsupporting

confidence: 59%

β-endorphin regulates alcohol consumption induced by exercise restriction in female mice

McGonigle

Nentwig

Wilson

et al. 2016

Alcohol

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“…Rat studies indicate that whereas μ-opioids in the VTA increase cortical and striatal DA, κ-opioids inhibit striatal dopamine, since NTX blocks both receptors, its effect on cortical DA levels is uncertain (Herz, 1995; Margolis et al, 2006; Spanagel et al, 1992) and could depend on the relative level of μ-versus κ-mediated actions. Relative μ-versus κ-effects would be expected to differ in subjects with low circulating levels of endogenous μ-receptor ligands, such as alcoholics and their off-spring (Dai et al, 2005; del Arbol et al, 1995; Govoni et al, 1983; Vescovi et al, 1992), or in those with low levels of μ-receptor expression, as is found in subjects with low frontal DA levels due to their COMT genotype (Berthele et al, 2005), and in subjects with the A118G polymorphism of the μ-opioid receptor (Zhang et al, 2005). Combining PET imaging of NTX binding with behavioral studies of immediate reward bias shifts may shed light on this issue.…”

Section: Discussionmentioning

confidence: 99%

Now or Later? An fMRI study of the effects of endogenous opioid blockade on a decision-making network

Boettiger

Kelley

Mitchell

et al. 2009

Pharmacology Biochemistry and Behavior

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Previously, we found that distinct brain areas predict individual selection bias in decisions between small immediate (“Now”) and larger delayed rewards (“Later”). Furthermore, such selection bias can be manipulated by endogenous opioid blockade. To test whether blocking endogenous opioids with Naltrexone (NTX) alters brain activity during decision-making in areas predicting individual bias, we compared fMRI BOLD signal correlated with Now versus Later decision-making after acute administration of NTX (50 mg) or placebo. We tested abstinent alcoholics and control subjects in a double-blind two-session design. We defined regions of interest (ROI) centered on activation peaks predicting Now versus Later selection bias. NTX administration significantly increased BOLD signal during decision-making in the right lateral orbital gyrus ROI, an area where enhanced activity during decision-making predicts Later bias. Exploratory analyses identified additional loci where BOLD signal during decision-making was enhanced (left orbitofrontal cortex, left inferior temporal gyrus, and cerebellum) or reduced (right superior temporal pole) by NTX. Additional analyses identified sites, including the right lateral orbital gyrus, in which NTX effects on BOLD signal predicted NTX effects on selection bias. These data agree with opioid receptor expression in human frontal and temporal cortices, and suggest possible mechanisms of NTX’s therapeutic effects.

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“…Given that NTX acts at both m-and k-opioid receptors, which exert opposing effects on forebrain DA release (Spanagel et al, 1992;Herz and Spangel, 1995;Margolis et al, 2006), differential effects of NTX on DA levels could be due to differences in relative m-and k-mediated effects of NTX, as depicted in Figure 6. Relative m-receptor to k-receptor blockade effects would be expected to differ in subjects with low circulating levels of endogenous m-receptor ligands, as is the case with alcoholics and their offspring (Govoni et al, 1983;Vescovi et al, 1992;del Arbol et al, 1995;Dai et al, 2005), or in subjects with low levels of m-receptor expression, as is found in subjects with low frontal DA levels (Berthele et al, 2005) owing to their catechol-O-methyltransferase genotype (Meyer-Lindenberg et al, 2005), and in subjects with the A118G polymorphism of the m-receptor (Zhang et al, 2005). This latter polymorphism has also shown a functional differentiation in the therapeutic response to NTX (Oslin et al, 2003), and has distinguished alcoholics from non-alcoholics in some populations (Bart et al, 2005).…”

Section: Discussion Ntx Effects On Impulsive Choicementioning

confidence: 99%

Endogenous Opioid Blockade and Impulsive Responding in Alcoholics and Healthy Controls

Mitchell

Fields

et al. 2006

Neuropsychopharmacol

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The opioid receptor antagonist naltrexone (NTX) is one of few approved treatments for alcoholism, yet the mechanism by which it reduces drinking remains unclear. In rats, NTX reduces morphine-induced impulsive choice bias; however, nothing is known about the drug's effect on discrete aspects of impulsive behavior in humans, such as decision-making and inhibitory control. Here, we used a modified delay discounting procedure to investigate whether NTX improves decision-making or inhibitory control in humans. We measured the effect of acute NTX (50 mg) on choice between smaller sooner (SS) and larger later monetary rewards and on response errors (motor mismatch) in a high conflict condition in a group of abstinent alcoholics (AA) and healthy control subjects (CS). We previously reported that AA selected the SS option significantly more often than did CS in this paradigm. If the choice bias of AA is due to enhanced endogenous opioid signaling in response to potential reward, NTX should reduce such bias in the AA group. We found that NTX did not reliably reduce impulsive choice in the AA group; however, NTX's effect on choice bias across individuals was robustly predictable. NTX's effect on choice bias was significantly correlated with scores on Rotter's Locus of Control (LOC) scale; increasingly internal LOC scores predicted increasing likelihood of impulsive choices on NTX. In addition, we found that NTX significantly enhanced control of motor responses, particularly within the CS group. These results suggest that endogenous opioids may impair response selection during decision-making under conflict, and that NTX's effects on explicit decision-making are personality-dependent. Determining the biological basis of this dependence could have important implications for effective alcoholism treatment.

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Plasma concentrations of β-endorphin, adrenocorticotropic hormone, and cortisol in drinking and abstinent chronic alcoholics

Cited by 31 publications

References 37 publications

β-endorphin regulates alcohol consumption induced by exercise restriction in female mice

β-endorphin regulates alcohol consumption induced by exercise restriction in female mice

Now or Later? An fMRI study of the effects of endogenous opioid blockade on a decision-making network

Endogenous Opioid Blockade and Impulsive Responding in Alcoholics and Healthy Controls

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