Accelerated habit formation following amphetamine exposure is reversed by D1, but enhanced by D2, receptor antagonists

Nelson, Andrew John Dudley; Killcross, Simon

doi:10.3389/fnins.2013.00076

Cited by 75 publications

(59 citation statements)

References 66 publications

(76 reference statements)

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“…Systemic data have shown opposing roles for dopamine D1 and D2 receptors on amphetamine-induced acceleration of habit formation. Systemic administration of dopamine D1 antagonists reverse this acceleration, although D2 antagonists facilitate habit formation, potentially consistent with data from the IL (Nelson and Killcross 2013). While PL dopamine signaling has been shown to modulate behavior in a response conflict paradigm (Haddon and Killcross 2011b), to our knowledge, the effect of IL dopamine manipulations on the regulation of context-specific behavior has not yet been investigated.…”

Section: Infralimbic Pfc Controls Extinction Of Instrumental and Pavlsupporting

confidence: 70%

A unifying model of the role of the infralimbic cortex in extinction and habits

2014

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The infralimbic prefrontal cortex (IL) has been shown to be critical for the regulation of flexible behavior, but its precise function remains unclear. This region has been shown to be critical for the acquisition, consolidation, and expression of extinction learning, leading many to hypothesize that IL suppresses behavior as part of a "stop" network. However, this framework is at odds with IL function in habitual behavior in which the IL has been shown to be required for the expression and acquisition of ongoing habitual behavior. Here, we will review the current state of knowledge of IL anatomy and function in behavioral flexibility and provide a testable framework for a single IL mechanism underlying its function in both extinction and habit learning.Addiction is characterized both by the inability to terminate or reduce drug taking even in the face of adverse consequences and by chronic relapse to drug taking. Investigation into the neurobiological substrates of the loss of behavioral flexibility in addiction has relied heavily on animal models of addictive behavior, including habit and extinction learning paradigms that investigate distinct components of inflexible behavior.The prefrontal cortex (PFC) has repeatedly been identified as critical for the cognitive control of flexible actions (Jentsch and Taylor 1999;Everitt et al. 2008;George and Koob 2010;Willcocks and McNally 2012). Subregions of the PFC have distinct connectivity that likely underlies their separable roles in behavior. The infralimbic PFC (IL) has been shown to have a unique role in the development and expression of inflexible reward seeking. Interestingly, IL has been shown to have opposing effects on behavior when compared with the adjacent prelimbic PFC (PL) or, more broadly, the dorsomedial PFC (dmPFC). Perhaps most surprising are the apparently contradictory roles of IL in different measures of behavioral flexibility. In the current review, we discuss models of inflexible drug seeking and the role of IL in the regulation of these behavioral processes. In particular, we focus on the precise function of IL in the acquisition and extinction of drug seeking and the development and expression of habitual drug-seeking behavior. We propose a framework for reconciling the seemingly contradictory role of IL in the regulation of flexible reward seeking through the suppression of the ability of established action-outcome contingencies to guide behavior.

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Section: Infralimbic Pfc Controls Extinction Of Instrumental and Pavlsupporting

confidence: 70%

A unifying model of the role of the infralimbic cortex in extinction and habits

2014

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“…When rats acquire instrumental responses for alcohol they become insensitive to devaluation earlier than when the outcome is pellets . Along the same lines, amphetamine pre-treatment speeds up the rate at which the outcome insensitivity develops (Nelson and Killcross, 2006), and this depends particularly on D 1 rather than D 2 receptors (Nelson and Killcross, 2013). In humans, there is evidence for enhanced habitization in obsessive-compulsive disorder (Everitt and Robbins, 2005;Robbins et al, 2012;Gillan et al, 2011Gillan et al, , 2013 and forthcoming evidence in cocaine addiction (N. Daw and V. Voon, personal communication), but not yet in alcohol addiction (Sebold et al, subm).…”

Section: Individual Variability In Addiction Vulnerabilitymentioning

confidence: 96%

The role of learning-related dopamine signals in addiction vulnerability

Huys

Tobler

Hasler

et al. 2014

Progress in Brain Research

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Psychostimulants such as methylphenidate (MPH) and antidepressants such as fluoxetine (FLX) are widely used in the treatment of various mental disorders or as cognitive enhancers. These medications are often combined, for example, to treat comorbid disorders. There is a considerable body of evidence from animal models indicating that individually these psychotropic medications can have detrimental effects on the brain and behavior, especially when given during sensitive periods of brain development. However, almost no studies investigate possible interactions between these drugs. This is surprising given that their combined neurochemical effects (enhanced dopamine and serotonin neurotransmission) mimic some effects of illicit drugs such as cocaine and amphetamine. Here, we summarize recent studies in juvenile rats on the molecular effects in the mid-and forebrain and associated behavioral changes, after such combination treatments. Our findings indicate that these combined MPH + FLX treatments can produce similar molecular changes as seen after cocaine exposure while inducing behavioral changes indicative of dysregulated mood and motivation, effects that often endure into adulthood. Tables: 2 References: 254 ABSTRACT Dopaminergic signals play a mathematically precise role in reward-related learning, and variations in dopaminergic signalling have been implicated in vulnerability to addiction. Here, we provide a detailed overview of the relationship between theoretical, mathematical and experimental accounts of phasic dopamine signalling, with implications for the role of learning-related dopamine signalling in addiction and related disorders. We describe the theoretical and behavioural characteristics of model-free learning based on errors in the prediction of reward, including step-by-step explanations of the underlying equations. We then use recent insights from an animal model that highlights individual variation in learning during a Pavlovian conditioning paradigm to describe overlapping aspects of incentive salience attribution and model-free learning. We argue that this provides a computationally coherent account of some features of addiction. CONTENTS

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“…related to dopamine D1 receptor activation(52). Selective nigrostriatal dopaminergic lesions impair habit formation(53).…”

mentioning

confidence: 99%