Individual Differences in Vulnerability to Drug Abuse: The High Responders/Low Responders Model

Kabbaj, Mohamed

doi:10.2174/187152706778559318

Cited by 72 publications

(67 citation statements)

References 56 publications

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“…The observation that glucocorticoids can modulate DA transmission (Piazza et al, 1993); the suggestion that HR rats have a deregulation of their HPA axis Kabbaj, 2006); and the relationship between GABA and DA within in the ACe (Marowsky et al, 2005) suggest that the differences in dopaminergic sensitivity between HR and LR rats (Marinelli and White, 2000;Chefer et al, 2003) are due to differences in ACe regulation of the HPA axis, and that inactivation of the ACe in HR rats may result in a change in HPA axis activation.…”

Section: Discussionmentioning

confidence: 99%

“…Further, social defeat stress increases cocaine self-administration in LR rats, but delays cocaine self-administration in HR rats (Kabbaj et al, 2001). One explanation for these seemingly conflicting results is that the increased vulnerability to drug abuse in HR rats is due to a deregulation of the HPA axis that results in hyperactivity of the mesolimbic dopamine system Kabbaj, 2006) and that perhaps the stress response itself is rewarding to HR rats .…”

Section: Discussionmentioning

confidence: 99%

“…In terms of translating this work to humans, it should be noted that the ability of the response to inescapable novelty to predict individual differences in drug use vulnerability is well established (Marinelli, 2005;Kabbaj, 2006). However, it is still uncertain if the response to inescapable novelty is a valid animal model of sensation seeking.…”

Section: Discussionmentioning

confidence: 99%

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Individual Differences in Amphetamine Self-Administration: The Role of the Central Nucleus of the Amygdala

Cain

Denehy

Bardo

2007

Neuropsychopharmacol

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Rats categorized as high responder (HR), based on their activity in an inescapable novel environment, self-administer more amphetamine than low responder (LR) rats. The current study examined if the central nucleus of the amygdala (ACe) contributes to the elevated response for amphetamine in HR rats. Male Sprague-Dawley rats were classified as HR and LR rats based on their activity in inescapable novelty and novelty place preference, and then were trained to self-administer amphetamine (0.1 mg/kg/infusion). Once stable responding was achieved, rats received microinfusions of the GABA A agonist muscimol (0.5 mg/0.5 ml) or phosphate-buffered saline into the ACe immediately before self-administration of amphetamine (0.1, 0.03, 0.01, or 0.001 mg/kg/infusion) or saline. An additional group of rats was trained to lever press for sucrose rather than amphetamine. Based on the inescapable novelty test, HR rats self-administered more amphetamine than LR rats at the 0.03 and 0.01 mg/kg/infusion unit doses; there were no significant individual differences in amphetamine self-administration based on the novelty place preference test. Inactivation of the ACe with muscimol decreased selfadministration at the 0.03 and 0.01 mg/kg/infusion unit doses in HR rats, but had no effect on LR rats. ACe inactivation had no reliable effect on inactive lever responding and appeared to be region specific based on anatomical controls. In addition, while inactivation of the ACe decreased responding for sucrose, inactivation did not differentially affect HR and LR rats. These results suggest that the ACe contributes to the elevated rate of amphetamine self-administration in HR rats.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Individual Differences in Amphetamine Self-Administration: The Role of the Central Nucleus of the Amygdala

Cain

Denehy

Bardo

2007

Neuropsychopharmacol

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“…Planned comparisons of main effects were employed and justified given the a priori hypothesized greater vulnerability to cocaine (degree of cocaine sensitization) of HR relative to LR phenotype (Kabbaj, 2006) regardless of the presence of significant two-way interaction terms.…”

Section: Data and Statistical Analysismentioning

confidence: 99%

“…Interestingly, the basal changes in FADD/ pFADD protein content were positively and negatively correlated, respectively, with the rats' rates of locomotion activity in a novel environment, suggesting the FADD system as a possible molecular correlate for the HR/LR phenotype. In addition to differences in sensitivity to psychostimulants (Piazza et al, 1989;Piazza and Le Moal, 1996; reviewed in Kabbaj, 2006), HR/LR animals display a variety of other behavioral differences including differences in anxiety behavior (Stead et al, 2006). Thus, future studies will focus on evaluating other behavioral or neuroendocrine measures to determine how they may relate to FADD levels.…”

Section: Regulation Of Fadd By Cocaine M-j García-fuster Et Almentioning

confidence: 99%

Effect of Cocaine on Fas-Associated Protein with Death Domain in the Rat Brain: Individual Differences in a Model of Differential Vulnerability to Drug Abuse

García-Fuster

Clinton

Watson

et al. 2008

Neuropsychopharmacol

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This study was designed to (1) assess the effects of cocaine on Fas-associated protein with death domain (FADD) system and its role in the activation of apoptotic vs nonapoptotic events and (2) ascertain whether animals selectively bred for their differential propensity to drug-seeking show differences in FADD levels or response to cocaine. Acute cocaine, through D 2 dopamine receptors, induced a doseresponse increase in FADD protein in the cortex, with opposite effects over pFADD (Ser191/194), and no induction of apoptotic cell death (poly-(ADP-ribose) polymerase cleavage). FADD was increased by cocaine in cytosol (B142%), membranes (B23%) and nucleus (B54%). The modulation of the FADD system showed tolerance of the acute effect over time, as well as a compensatory response on withdrawal that mirrored the acute effectFie a transient FADD decrease on day 3 of withdrawal, both at mRNA and protein levels. In a second experiment, possible FADD differences were investigated in rats selectively bred for differential responsiveness to novelty, propensity for drug-seeking and cocaine sensitization. High-responders (HR), who were more prone to drug abuse, exhibited higher FADD and lower pFADD levels than low-responder (LR) rats. However, HR and LR rats showed similar rates of cocaine-induced apoptosis, and exhibited a parallel impact of cocaine over FADD within each phenotype. Thus, FADD is a signaling protein modulated by cocaine, regulating apoptosis/proliferative mechanisms in relation to its FADD/pFADD content. Interestingly, animals selectively bred for differential propensity to substance abuse show basal differences in the expression of this protein, suggesting FADD may also be a molecular correlate for the HR/LR phenotype.

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Predictors of social instability stress effects on social interaction and anxiety in adolescent male rats

Hodges

Baumbach

McCormick

2018

Developmental Psychobiology

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Adolescence is an important phase of development of social behaviors, which may be disrupted by the experience of stressors. We previously reported that exposure to social instability stress in adolescence (SS; postnatal day [PND] 30–45) in rats reduced social interactions with unfamiliar peers compared with non‐stressed controls (CTL). In experiment 1, we replicated the effect of SS on social interaction and found that the pattern of neural activations based on Fos immunohistochemistry in brain regions during social interactions differed for SS and CTL rats. In experiment 2, we found that individual differences in novelty‐seeking behavior on PND 30 and SS exposure were unique predictors of anxiety in the elevated plus maze on PND 46, and interacted to predict social interaction on PND 47; among high novelty‐seeking rats, SS and CTL rats do not differ, whereas among low‐novelty seeking rats, SS rats engaged in less social interaction than did CTL rats. Thus, high novelty‐seeking may be a resilience factor against the effects of social stressors in adolescence.

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Individual Differences in Vulnerability to Drug Abuse: The High Responders/Low Responders Model

Cited by 72 publications

References 56 publications

Individual Differences in Amphetamine Self-Administration: The Role of the Central Nucleus of the Amygdala

Individual Differences in Amphetamine Self-Administration: The Role of the Central Nucleus of the Amygdala

Effect of Cocaine on Fas-Associated Protein with Death Domain in the Rat Brain: Individual Differences in a Model of Differential Vulnerability to Drug Abuse

Predictors of social instability stress effects on social interaction and anxiety in adolescent male rats

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