Dopamine D1/D5 receptors in the dorsal hippocampus are required for the acquisition and expression of a single trial cocaine-associated memory

Kramar, Cecilia P.; Barbano, M. Flavia; Medina, Jorge H.

doi:10.1016/j.nlm.2014.10.004

Cited by 26 publications

(27 citation statements)

References 65 publications

(90 reference statements)

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“…We report an inverse relationship between hippocampal CRH and DRD1 expression, a relationship which is further exaggerated in Sub mice under stress or drug exposure, but this stress response does not appear to exist in Dom mice. Hippocampus functions in reinforcement of attraction and aversion to novel and salient stimuli, driven by DRD1/DRD5-dependent mechanisms 19 , 40 – 43 , 52 . Dopamine receptor downregulation as a result of stress would tend to increase salient memory encoding as a result of receptor saturation and following drug exposure would tend to reinforce drug attraction, thus aiding mesolimbic circuits driving drug use reinstatement 53 – 56 .…”

Section: Discussionmentioning

confidence: 99%

Social rank-associated stress vulnerability predisposes individuals to cocaine attraction

Yanovich

Kirby

Michaelevski

et al. 2018

Sci Rep

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Studies of personality have suggested that dissimilarities in ability to cope with stressful situations results in differing tendency to develop addictive behaviors. The present study used selectively bred stress-resilient, socially-dominant (Dom) and stress-vulnerable, socially-submissive (Sub) mice to investigate the interaction between environmental stress and inbred predisposition to develop addictive behavior to cocaine. In a Conditioned Place Preference (CPP) paradigm using cocaine, Sub mice displayed an aversion to drug, whereas Dom mice displayed drug attraction. Following a 4-week regimen of Chronic Mild Stress (CMS), Sub mice in CPP displayed a marked increase (>400%) in cocaine attraction, whereas Dom mice did not differ in attraction from their non-stressed state. Examination of hippocampal gene expression revealed in Sub mice, exposure to external stimuli, stress or cocaine, increased CRH expression (>100%), which was evoked in Dom mice only by cocaine exposure. Further, stress-induced decreases in DRD1 (>60%) and DRD2 (>50%) expression in Sub mice differed markedly from a complete lack of change in Dom mice. From our findings, we propose that social stratification dictates vulnerability to stress-induced attraction that may lead to addiction via differential regulation of hippocampal response to dopaminergic input, which in turn may influence differing tendency to develop addictive behaviors.Ready availability of a variety of narcotic substances coupled with abundant 21-century stressors has markedly increased drug use and produced accompanying social problems of a grave nature 1,2 . There is literature evidence of the significant association between personality, stress and the motivation to abuse addictive substances [3][4][5] . The ability of individuals to cope effectively with stress significantly predicts whether a person will develop drug addiction 4 .Results of personality studies in humans and animal models have suggested that differences exist with respect to stress responses based on coping style 6 . Socially dominant individuals display a stress resilience, typified by proactive behaviors 7,8 . One such proactive behavior is impulsiveness, which has been linked as a vulnerability factor to substance abuse in both clinical and preclinical studies 9 . In contrast, subordinate individuals are more prone to develop depression 10,11 and under conditions of stress from trauma or social defeat have a tendency to engage in social avoidance behaviors and migrate to self-indulgent coping styles such as substance abuse 12 . The underlying drivers of these baseline coping strategies and responses have been assumed to reside within functioning of the limbic system, prominently mediated by baseline mesolimbic dopaminergic tone, with impulsive individuals displaying low baseline dopaminergic output and non-impulsive individuals displaying high baseline dopaminergic output 13 . Not to be excluded, the hippocampus and associated memory circuits also play an important role in reinforcement of memories, re...

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Section: Discussionmentioning

confidence: 99%

Social rank-associated stress vulnerability predisposes individuals to cocaine attraction

Yanovich

Kirby

Michaelevski

et al. 2018

Sci Rep

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“…Because CPP is contingent upon an animal associating the rewarding/aversive properties of a drug with environmental cues, areas of the brain that are essential for memory associations of contextual stimuli, such as the ventral tegmental area and hippocampal formation 19 20 21 22 , are likely to play a role in the behaviors observed. In particular, the hippocampus has been shown to be a key mediator for the acquisition and expression of cocaine CPP 20 23 . In addition to being crucial for drug-related contextual memories 24 25 26 , the hippocampus has also been a site of FLX-induced alterations of signaling molecules associated with antidepressant efficacy 27 .…”

Section: Discussionmentioning

confidence: 99%

Fluoxetine exposure during adolescence increases preference for cocaine in adulthood

Iñiguez

Riggs

Nieto

et al. 2015

Sci Rep

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Currently, there is a high prevalence of antidepressant prescription rates within juvenile populations, yet little is known about the potential long-lasting consequences of such treatments, particularly on subsequent responses to drugs of abuse. To address this issue at the preclinical level, we examined whether adolescent exposure to fluoxetine (FLX), a selective serotonin reuptake inhibitor, results in changes to the sensitivity of the rewarding properties of cocaine in adulthood. Separate groups of male c57bl/6 mice were exposed to FLX (0 or 20 mg/kg) for 15 consecutive days either during adolescence (postnatal days [PD] 35–49) or adulthood (PD 65–79). Twenty-one days after FLX treatment, behavioral responsivity to cocaine (0, 2.5, 5, 10, or 20 mg/kg) conditioned place preference was assessed. Our data shows that mice pretreated with FLX during adolescence, but not during adulthood, display an enhanced dose-dependent preference to the environment paired with cocaine (5 or 10 mg/kg) when compared to age-matched saline pretreated controls. Taken together, our findings suggest that adolescent exposure to FLX increases sensitivity to the rewarding properties of cocaine, later in life.

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“…( 13 )]. The dorsal hippocampus appears to have a role in the contextual control of drug seeking for cocaine ( 14 – 16 ). The lateral region of the dorsal striatum (DLS) mediates S–R habitual lever pressing for cocaine and alcohol ( 17 , 18 ), and the basolateral amygdala (BLA) mediates conditioned drug seeking for cocaine, alcohol, and heroin ( 19 – 22 ).…”

Section: The Multiple Memory Systems View Of Addictionmentioning

confidence: 99%

Memory Systems and the Addicted Brain

2016

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The view that anatomically distinct memory systems differentially contribute to the development of drug addiction and relapse has received extensive support. The present brief review revisits this hypothesis as it was originally proposed 20 years ago (1) and highlights several recent developments. Extensive research employing a variety of animal learning paradigms indicates that dissociable neural systems mediate distinct types of learning and memory. Each memory system potentially contributes unique components to the learned behavior supporting drug addiction and relapse. In particular, the shift from recreational drug use to compulsive drug abuse may reflect a neuroanatomical shift from cognitive control of behavior mediated by the hippocampus/dorsomedial striatum toward habitual control of behavior mediated by the dorsolateral striatum (DLS). In addition, stress/anxiety may constitute a cofactor that facilitates DLS-dependent memory, and this may serve as a neurobehavioral mechanism underlying the increased drug use and relapse in humans following stressful life events. Evidence supporting the multiple systems view of drug addiction comes predominantly from studies of learning and memory that have employed as reinforcers addictive substances often considered within the context of drug addiction research, including cocaine, alcohol, and amphetamines. In addition, recent evidence suggests that the memory systems approach may also be helpful for understanding topical sources of addiction that reflect emerging health concerns, including marijuana use, high-fat diet, and video game playing.

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Dopamine D1/D5 receptors in the dorsal hippocampus are required for the acquisition and expression of a single trial cocaine-associated memory

Cited by 26 publications

References 65 publications

Social rank-associated stress vulnerability predisposes individuals to cocaine attraction

Social rank-associated stress vulnerability predisposes individuals to cocaine attraction

Fluoxetine exposure during adolescence increases preference for cocaine in adulthood

Memory Systems and the Addicted Brain

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