Effects of morphine and naltrexone on impulsive decision making in rats

Kieres, Artur K.; Hausknecht, Kathryn A.; Farrar, Andrew M.; Acheson, Ashley; Wit, Harriet de; Richards, Jerry B.

doi:10.1007/s00213-003-1697-2

Cited by 86 publications

(83 citation statements)

References 42 publications

(45 reference statements)

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“…Effects of 0.5 mg/kg amphetamine, intracranial naloxone into the NAc shell and NAc core subregions and their combination, or intracranial morphine into the NAc shell and NAc core subregions on measures of attentional function, compulsivity, and motivation in the 5-CSRTT receptors would be expected to potentiate rather than reduce amphetamineinduced DA release and subsequent impulsive decisions. Interestingly, there is ample evidence linking the opioid system, particularly -opioid receptors, to regulation of impulsive decision making (Kieres et al, 2004;Mitchell et al, 2007;Boettiger et al, 2009;Love et al, 2009;Pattij et al, 2009). It can therefore be concluded that (1) psychostimulants alter impulsive choice via opioid-independent mechanisms and (2) opioids may modify this behavior via distinct neuronal mechanisms.…”

Section: Opioids Amphetamine and Impulsive Choicementioning

confidence: 99%

“…Although the effects of amphetamine on impulsivity depend on enhanced dopamine (DA) transmission Robbins, 1987, 1989;Winstanley et al, 2003Winstanley et al, , 2005van Gaalen et al, 2006bvan Gaalen et al, , 2009Pattij et al, 2007), other neurotransmitter systems may also play crucial roles in regulating impulsive behavior, including endogenous opioid systems (Madden et al, 1997;Kieres et al, 2004;Mitchell et al, 2007;Boettiger et al, 2009;Love et al, 2009;Olmstead et al, 2009;Pattij et al, 2009;Zacny and de Wit, 2009). Indeed, there is ample evidence showing that amphetamine activates endogenous opioid systems McGinty, 1995, 1996;Olive et al, 2001;Gonzalez-Nicolini et al, 2003), and the effects of amphetamine on DA release and behavioral measures including locomotion, reward, and amphetamine-induced rein-statement of amphetamine seeking involve opioid transmission (Trujillo et al, 1991;Hooks et al, 1992;Schad et al, 1995;Jayaram-Lindström et al, 2004Häggkvist et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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μ-Opioid Receptors in the Nucleus Accumbens Shell Region Mediate the Effects of Amphetamine on Inhibitory Control But Not Impulsive Choice

Wiskerke

Schetters

Es³

et al. 2011

J. Neurosci.

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Acute challenges with psychostimulants such as amphetamine affect impulsive behavior in both animals and humans. With regard to amphetamine, it is important to unravel how this drug affects impulsivity since it is not only a widely abused recreational drug but also regularly prescribed to ameliorate maladaptive impulsivity. Therefore, we studied the effects of amphetamine in two rat models of impulsivity, the five-choice serial reaction time task and the delayed-reward task, providing measures of inhibitory control and impulsive choice, respectively. We focused on the role of opioid receptor activation in amphetamine-induced impulsivity as there is ample evidence indicating an important role for endogenous opioids in several behavioral and neurochemical effects of amphetamine. Results showed that amphetamine-induced inhibitory control deficits were dose-dependently attenuated by the preferential -opioid receptor antagonist naloxone, but not by the selective ␦-opioid receptor antagonist naltrindole or -opioid receptor antagonist nor-BNI (norbinaltorphimine dihydrochloride). In contrast, naloxone did not affect amphetamine-induced improvements in impulsive decision making. Naloxone also completely prevented inhibitory control deficits induced by GBR -ol]-enkephalin acetate salt) revealed that -opioid receptor activation in the shell rather than the core subregion of the nucleus accumbens (NAc) modulates inhibitory control and subserves the effect of amphetamine thereon. Together, these results indicate an important role for NAc shell -opioid receptors in the regulation of inhibitory control, probably via an interaction between these receptors and the mesolimbic dopamine system.

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Section: Opioids Amphetamine and Impulsive Choicementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

μ-Opioid Receptors in the Nucleus Accumbens Shell Region Mediate the Effects of Amphetamine on Inhibitory Control But Not Impulsive Choice

Wiskerke

Schetters

Es³

et al. 2011

J. Neurosci.

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“…With regard to the modulation of inhibitory control per se, however, opioids have received comparatively little attention. A small number of systemic pharmacology and gene knockout studies have shown that μ-opioid receptor (μOR) signaling promotes impulsivity; however, the brain sites underlying this effect are not fully known (Kieres et al, 2004;Mahoney et al, 2013;Olmstead et al, 2009;Pattij et al, 2009). To date, the possibility that endogenous opioids act within frontal cortex to modulate (or provoke) impulsive reward-seeking action has never been explored.…”

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

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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.

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“…This hypothesis is supported by animal studies that have shown NTX to be effective at decreasing impulsive choice bias. For example, in rats, NTX reverses a morphine induced increase in preference for small immediate rewards over larger delayed rewards (Kieres et al, 2004). Moreover, in humans, NTX attenuates a variety of impulse disorders, including pathological gambling (Kim et al, 2001), binge eating in bulimics (Marrazzi et al, 1995), compulsive sexual behavior (Raymond et al, 2002), self-injurious behavior (Symons et al, 2004), and kleptomania (Grant, 2005).…”

Section: Introductionmentioning

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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Effects of morphine and naltrexone on impulsive decision making in rats

Abstract: These results suggested that the direct effects of MOR may contribute to the high level of impulsive behavior seen among opiate users.

Cited by 86 publications

References 42 publications

μ-Opioid Receptors in the Nucleus Accumbens Shell Region Mediate the Effects of Amphetamine on Inhibitory Control But Not Impulsive Choice

μ-Opioid Receptors in the Nucleus Accumbens Shell Region Mediate the Effects of Amphetamine on Inhibitory Control But Not Impulsive Choice

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

Endogenous Opioid Blockade and Impulsive Responding in Alcoholics and Healthy Controls

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