The strength of aversive and appetitive associations and maladaptive behaviors

Itzhak, Yossef; Perez-Lanza, Daniel; Liddie, Shervin

doi:10.1002/iub.1310

Cited by 17 publications

(11 citation statements)

References 102 publications

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“…Beyond hemispatial learning, the present results may also have clinical implications. Specifically, some individuals are at higher risk of developing mental disorders (Chambers et al, 2004;Indovina et al, 2011), and recent evidence links the development and maintenance of mental disorders to biased learning processes (Itzhak et al, 2014;Mineka and Oehlberg, 2008). Therefore, studying individual differences in the neural mechanisms underlying learning may be relevant for understanding why some individuals may be more likely than others to develop mental disorders.…”

Section: Resultsmentioning

confidence: 99%

The left hemisphere learns what is right: Hemispatial reward learning depends on reinforcement learning processes in the contralateral hemisphere

2016

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a b s t r a c tOrienting biases refer to consistent, trait-like direction of attention or locomotion toward one side of space. Recent studies suggest that such hemispatial biases may determine how well people memorize information presented in the left or right hemifield. Moreover, lesion studies indicate that learning rewarded stimuli in one hemispace depends on the integrity of the contralateral striatum. However, the exact neural and computational mechanisms underlying the influence of individual orienting biases on reward learning remain unclear. Because reward-based behavioural adaptation depends on the dopaminergic system and prediction error (PE) encoding in the ventral striatum, we hypothesized that hemispheric asymmetries in dopamine (DA) function may determine individual spatial biases in reward learning. To test this prediction, we acquired fMRI in 33 healthy human participants while they performed a lateralized reward task. Learning differences between hemispaces were assessed by presenting stimuli, assigned to different reward probabilities, to the left or right of central fixation, i.e. presented in the left or right visual hemifield. Hemispheric differences in DA function were estimated through differential fMRI responses to positive vs. negative feedback in the left vs. right ventral striatum, and a computational approach was used to identify the neural correlates of PEs. Our results show that spatial biases favoring reward learning in the right (vs. left) hemifield were associated with increased reward responses in the left hemisphere and relatively better neural encoding of PEs for stimuli presented in the right (vs. left) hemifield. These findings demonstrate that trait-like spatial biases implicate hemispherespecific learning mechanisms, with individual differences between hemispheres contributing to reinforcing spatial biases.

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Section: Resultsmentioning

confidence: 99%

The left hemisphere learns what is right: Hemispatial reward learning depends on reinforcement learning processes in the contralateral hemisphere

2016

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“…We also demonstrated that even in DSI counterconditioned mice, a subsequent cocaine history that is long enough (i.e., four 15 min cocaine conditioning sessions) is sufficient to overcome the protective effect of DSI. Our findings also suggest that both the reversal of CPP from cocaine to DSI as well as that from DSI to cocaine, i.e., counterconditioning in either case, requires a learning process spanning four conditioning sessions (and not only a single one), regardless of the nature (i.e., cocaine as a prototypical drug of abuse vs. DSI as a physiologic stimulus) or the attractiveness of the initial stimulus (for critical evaluations of stimulus strength in various CPP procedures see e.g., Bardo et al, 1995 , 2013 ; Bardo and Bevins, 2000 ; Tzschentke, 2007 ; Itzhak et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Preventive Strength of Dyadic Social Interaction against Reacquisition/Reexpression of Cocaine Conditioned Place Preference

Bregolin

Pinheiro

Rawas

et al. 2017

Front. Behav. Neurosci.

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The reorientation away from drugs of abuse and toward social interaction is a highly desirable but as yet elusive goal in the therapy of substance dependence. We could previously show that cocaine preferring Sprague-Dawley rats which engaged in only four 15 min episodes of dyadic social interaction (DSI) did not reacquire and reexpress cocaine conditioned place preference (CPP) after a single cocaine exposure. In the present study, we investigated how strong this preventive effect of DSI is. In corroboration of our previous findings in rats, four 15 min DSI episodes prevented the reacquisition/reexpression of cocaine CPP in mice. However, this effect was only observed if only one cocaine conditioning session (15 min) was used. If mice were counterconditioned with a total of four cocaine sessions, the cocaine CPP reemerged. Interestingly, the opposite also held true: in mice that had acquired/expressed cocaine CPP, one conditioning session with DSI did not prevent the persistence of cocaine CPP, whereas four DSI conditioning sessions reversed CPP for 15 mg/kg intraperitoneal cocaine. Of note, this cocaine dose was a strong reward in C57BL/6J mice, causing CPP in all tested animals. Our findings suggest that both the reversal (reconditioning) of CPP from cocaine to DSI as well as that from DSI to cocaine requires four conditioning sessions. As previously shown in C57BL/6 mice from the NIH substrain, mice from the Jackson substrain also showed a greater relative preference for 15 mg/kg intraperitoneal cocaine over DSI, whereas Sprague-Dawley rats were equally attracted to contextual stimuli associated with this cocaine dose and DSI. Also in corroboration of previous findings, both C57BL/6J mice and experimenters several generations removed from the original ones produced CPP for DSI to a lesser degree than Sprague-Dawley rats. Our findings demonstrate the robustness of our experimental model across several subject- and experimenter generations in two rodent genus (i.e., mouse and rat) and allow the quantification of the strength (i.e., persistence) of the preventive effect of DSI against the reacquisition/reexpression of cocaine CPP, arguably a model for cocaine relapse.

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“…In the cocaine-induced CPP model, appetitive context is associated with drug reward effect, which will elicit a conditioned response after conditioning. The conditioned response is strongly dependent on the strength of the LTM of the association between appetitive context and drug effect ( Itzhak et al, 2014 ). Cocaine self-administration is also dependent on reinforcement learning, whereas an operant behavior is involved in this process, which makes it completely different from the CPP behavior ( Aguilar et al, 2009 ; Sorg, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of Trace Amine-associated Receptor 1 Agonists on the Expression, Reconsolidation, and Extinction of Cocaine Reward Memory

Liu

Thorn

Zhang

et al. 2016

IJNPPY

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Background:As a modulator of dopaminergic system, trace amine-associated receptor 1 has been shown to play a critical role in regulating the rewarding properties of additive drugs. It has been demonstrated that activation of trace amine-associated receptor 1 decreased the abuse-related behaviors of cocaine in rats. However, the role of trace amine-associated receptor 1 in specific stages of cocaine reward memory is still unclear.Methods:Here, using a cocaine-induced conditioned place preference model, we tested the effects of a selective trace amine-associated receptor 1 agonist RO5166017 on the expression, reconsolidation, and extinction of cocaine reward memory.Results:We found that RO5166017 inhibited the expression but not retention of cocaine-induced conditioned place preference. RO5166017 had no effect on the reconsolidation of cocaine reward memory. Pretreatment with RO5166017 before extinction hindered the formation of extinction long-term memory. RO5166017 did not affect the movement during the conditioned place preference test, indicating the inhibitory effect of RO5166017 on the expression of cocaine-induced conditioned place preference was not caused by locomotion inhibition. Using a cocaine i.v. self-administration model, we found that the combined trace amine-associated receptor 1 partial agonist RO5263397 with extinction had no effect on the following cue- and drug-induced reinstatement of cocaine-seeking behavior. Repeated administration of the trace amine-associated receptor 1 agonist during extinction showed a continually inhibitory effect on the expression of cocaine reward memory both in cocaine-induced conditioned place preference and cocaine self-administration models.Conclusions:Taken together, these results indicate that activation of trace amine-associated receptor 1 specifically inhibited the expression of cocaine reward memory. The inhibitory effect of trace amine-associated receptor 1 agonists on cocaine reward memory suggests that trace amine-associated receptor 1 agonists could be a promising agent to prevent cocaine relapse.

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The strength of aversive and appetitive associations and maladaptive behaviors

Cited by 17 publications

References 102 publications

The left hemisphere learns what is right: Hemispatial reward learning depends on reinforcement learning processes in the contralateral hemisphere

The left hemisphere learns what is right: Hemispatial reward learning depends on reinforcement learning processes in the contralateral hemisphere

Preventive Strength of Dyadic Social Interaction against Reacquisition/Reexpression of Cocaine Conditioned Place Preference

Effects of Trace Amine-associated Receptor 1 Agonists on the Expression, Reconsolidation, and Extinction of Cocaine Reward Memory

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