Abstract:Studies using the renewal procedure showed that basolateral amygdala (BLA) inactivation inhibits context-induced relapse to cocaineseeking after extinction. Here, we determined whether BLA inactivation would also inhibit context-induced relapse after drug-reinforced responding is suppressed by punishment, an animal model of human relapse after self-imposed abstinence due to adverse consequences of drug use. We also determined the effect of central amygdala (CeA) inactivation on context-induced relapse. We trai… Show more
“…These effects are reminiscent of the effects of extinction, leading to suggestions that punishment and extinction involve similar contextual learning processes. However, there is only partial overlap between the brain mechanisms of contextual control of punishment and extinction [ 41 , 42 ] and there are other important behavioral [ 43 ] and neurobiological [ 44 ] distinctions between them.…”
Section: Learning Processes Involved In Punishment Experimentsmentioning
confidence: 99%
“…The role of central nucleus of the amygdala (CeA) is less clear. Some studies show that CeA mediates Pavlovian but not punishment suppression [ 85 ], whereas others suggest a role in punishment of cocaine-seeking [ 44 , 86 ]. Fig.…”
Punishment involves learning about the relationship between behavior and its adverse consequences. Punishment is fundamental to reinforcement learning, decision-making and choice, and is disrupted in psychiatric disorders such as addiction, depression, and psychopathy. However, little is known about the brain mechanisms of punishment and much of what is known is derived from study of superficially similar, but fundamentally distinct, forms of aversive learning such as fear conditioning and avoidance learning. Here we outline the unique conditions that support punishment, the contents of its learning, and its behavioral consequences. We consider evidence implicating GABA and monoamine neurotransmitter systems, as well as corticostriatal, amygdala, and dopamine circuits in punishment. We show how maladaptive punishment processes are implicated in addictions, impulse control disorders, psychopathy, anxiety, and depression and argue that a better understanding of the cellular, circuit, and cognitive mechanisms of punishment will make important contributions to next generation therapeutic approaches.
“…These effects are reminiscent of the effects of extinction, leading to suggestions that punishment and extinction involve similar contextual learning processes. However, there is only partial overlap between the brain mechanisms of contextual control of punishment and extinction [ 41 , 42 ] and there are other important behavioral [ 43 ] and neurobiological [ 44 ] distinctions between them.…”
Section: Learning Processes Involved In Punishment Experimentsmentioning
confidence: 99%
“…The role of central nucleus of the amygdala (CeA) is less clear. Some studies show that CeA mediates Pavlovian but not punishment suppression [ 85 ], whereas others suggest a role in punishment of cocaine-seeking [ 44 , 86 ]. Fig.…”
Punishment involves learning about the relationship between behavior and its adverse consequences. Punishment is fundamental to reinforcement learning, decision-making and choice, and is disrupted in psychiatric disorders such as addiction, depression, and psychopathy. However, little is known about the brain mechanisms of punishment and much of what is known is derived from study of superficially similar, but fundamentally distinct, forms of aversive learning such as fear conditioning and avoidance learning. Here we outline the unique conditions that support punishment, the contents of its learning, and its behavioral consequences. We consider evidence implicating GABA and monoamine neurotransmitter systems, as well as corticostriatal, amygdala, and dopamine circuits in punishment. We show how maladaptive punishment processes are implicated in addictions, impulse control disorders, psychopathy, anxiety, and depression and argue that a better understanding of the cellular, circuit, and cognitive mechanisms of punishment will make important contributions to next generation therapeutic approaches.
“…This model is a modified ABA renewal procedure in which abstinence is achieved in context B, despite alcohol availability, by punishment with response-contingent electric footshock. Using this model, we have demonstrated context-induced relapse to both alcohol and cocaine seeking when rats were tested in context A after punishment-imposed abstinence in context B (Marchant et al 2014 , 2016 ; Marchant and Kaganovsky 2015 ; Pelloux et al 2018a , b ). Our model and findings extend previous research in the addiction field on the use of punishment procedures to model the negative consequences of drug seeking and drug use (Deroche-Gamonet et al 2004 ; Marchant et al 2013b ; Panlilio et al 2003 ; Pelloux et al 2007 ; Vanderschuren et al 2017 ; Vanderschuren and Everitt 2004 ; Wolffgramm and Heyne 1995 ).…”
Results from clinical studies suggest that drug relapse and craving are often provoked by exposure to drug-associated contexts. Since 2002, this phenomenon has been modeled in laboratory animals using the ABA renewal model. In the classical version of this model, rats with a history of drug self-administration in one context (A) undergo extinction in a different context (B) and reinstate (or relapse to) drug seeking after exposure to the original drug-associated context (A). In a more recent version of the model introduced in 2013, the experimental conditions in context A are identical to those used in the classical model, but drugreinforced responding in context B is suppressed by probabilistic punishment. The punishment-based ABA renewal model is proposed to resemble abstinence in humans, which is often initiated by the desire to avoid the negative consequences of drug use. The goal of our review is to discuss similarities and differences in mechanisms that play a role in suppression of drug seeking in context B and context-induced relapse to drug seeking in context A in the two models. We first describe psychological mechanisms that mediate extinction and punishment of drug-reinforced responding in context B. We then summarize recent findings on brain mechanisms of context-induced relapse of drug seeking after extinction, or punishment-imposed abstinence. These findings demonstrate both similarities and differences in brain mechanisms underlying relapse in the two variations of the ABA renewal model. We conclude by briefly discussing clinical implications of the preclinical studies.
“…For example, drug dependence can be attenuated via voluntary or forced abstinence [(Venniro et al 2016 ); although this is known to incubate the drug-seeking responses] as well as through punishment of the instrumental response (in which the drug-seeking behavior is instead paired with a noxious outcome) (Smith and Laiks 2017 ; Marchant et al 2018 ). The brain mechanisms of relapse may differ as a function of the procedure used to reduce responding (Pelloux et al 2018 ). Similarly, fear-conditioned responses can be reduced through counterconditioning procedures in which the CS is paired with a reward rather than the aversive US (Holmes et al 2016 ; Kang et al 2018 ); and this engages additional neural circuitry (Bulganin et al 2014 ; Correia et al 2016 ).…”
Section: Introductionmentioning
confidence: 99%
“…Similarly, gamma oscillations in the amygdala during extinction have been shown to correlate with levels of spontaneous recovery during retrieval (Courtin et al 2014 ) and electrical stimulation of the amygdala can induce fear relapse (Kellett and Kokkinidis 2004 ). In turn, the amygdala (including its BLA/CeA regions) is essential for both fear and drug relapse, such that lesions of the amygdala prevent fear renewal (Herry et al 2008 ), fear reinstatement (Laurent and Westbrook 2010 ), drug reinstatement (Meil and See 1997 ; Grimm and See 2000 ; Kantak et al 2002 ; Fuchs and See 2002 ; Yun and Fields 2003 ; Wang et al 2006 ; Rogers et al 2008 ; Cummins et al 2014 ; Li et al 2015 ), and drug renewal (Fuchs et al 2005a ; Fuchs et al 2007 ; Lasseter et al 2011 ; Wells et al 2013 ; Chaudhri et al 2013 ; Stringfield et al 2016 ; Pelloux et al 2018 ). Additionally, inactivation studies suggest that the CeA plays a critical role in stress-induced drug relapse [(Shaham et al 2000 ; McFarland et al 2004 ) also, see (Leri et al 2002 ; Wang et al 2006 ; Yamada and Bruijnzeel 2011 )].…”
Background
Comorbidity of anxiety disorders, stressor- and trauma-related disorders, and substance use disorders is extremely common. Moreover, therapies that reduce pathological fear and anxiety on the one hand, and drug-seeking on the other, often prove short-lived and are susceptible to relapse. Considerable advances have been made in the study of the neurobiology of both aversive and appetitive extinction, and this work reveals shared neural circuits that contribute to both the suppression and relapse of conditioned responses associated with trauma or drug use.
Objectives
The goal of this review is to identify common neural circuits and mechanisms underlying relapse across domains of addiction biology and aversive learning in preclinical animal models. We focus primarily on neural circuits engaged during the expression of relapse.
Key findings
After extinction, brain circuits involving the medial prefrontal cortex and hippocampus come to regulate the expression of conditioned responses by the amygdala, bed nucleus of the stria terminalis, and nucleus accumbens. During relapse, hippocampal projections to the prefrontal cortex inhibit the retrieval of extinction memories resulting in a loss of inhibitory control over fear- and drug-associated conditional responding.
Conclusions
The overlapping brain systems for both fear and drug memories may explain the co-occurrence of fear and drug-seeking behaviors.
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