The HR/LR model: Further evidence as an animal model of sensation seeking

Blanchard, Mathieu; Mendelsohn, Daniel; Stamp, Jennifer A.

doi:10.1016/j.neubiorev.2009.05.009

Cited by 106 publications

(106 citation statements)

References 135 publications

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“…have shown that a high impulsivity trait in the rat, as measured by an inability to withhold inappropriate responding in a five-choice serial reaction time test (5-CSRTT) (Bari et al 2008), predicts specifically, and exclusively, the switch to compulsive cocaine self-administration after protracted exposure to the drug. In this study, and as previously shown by Piazza et al (1989), sensation seeking, as measured by a high locomotor response to novelty (Blanchard et al 2009), predicted vulnerability to acquire self-administration for low cocaine doses, but was shown to be orthogonal to both a high impulsivity trait and the vulnerability to addiction-like behavior.…”

Section: Novelty Responses and Vulnerability To Addiction-like Behavisupporting

confidence: 79%

Responses to Novelty and Vulnerability to Cocaine Addiction: Contribution of a Multi-Symptomatic Animal Model

Belin

Deroche-Gamonet

2012

Cold Spring Harbor Perspectives in Medicine

122

113

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Epidemiological studies have revealed striking associations between several distinct behavioral/personality traits and drug addiction, with a large emphasis on the sensation-seeking trait and the associated impulsive dimension of personality. However, in human studies, it is difficult to identify whether personality/behavioral traits actually contribute to increased vulnerability to drug addiction or reflect psychobiological adaptations to chronic drug exposure. Here we show how animal models, including the first multi-symptomatic model of addiction in the rat, have contributed to a better understanding of the relationships between different subdimensions of the sensation-seeking trait and different stages of the development of cocaine addiction, from vulnerability to initiation of cocaine self-administration to the transition to compulsive drug intake. We argue that sensation seeking predicts vulnerability to use cocaine, whereas novelty seeking, akin to high impulsivity, predicts instead vulnerability to shift from controlled to compulsive cocaine use, that is, addiction.

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Section: Novelty Responses and Vulnerability To Addiction-like Behavisupporting

confidence: 79%

Responses to Novelty and Vulnerability to Cocaine Addiction: Contribution of a Multi-Symptomatic Animal Model

Belin

Deroche-Gamonet

2012

Cold Spring Harbor Perspectives in Medicine

122

113

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“…Intriguingly, decreased ACC glutamate concentrations in healthy subjects have been found to be associated with high levels of sensation-seeking behavior (Gallinat et al, 2007), which usually goes along with high risk taking and low levels of anxiety-related behavior according to preclinical studies (Blanchard et al, 2009). The fact that Glx concentrations show a fast and immediate increase following experimental panic induction suggests that apart from static alterations in glutamatergic neurotransmission outlined above rapid and dynamic neurochemical changes might also be important for the neural control of acute anxiety and panic attacks.…”

Section: Discussionmentioning

confidence: 99%

Acute Shift in Glutamate Concentrations Following Experimentally Induced Panic with Cholecystokinin Tetrapeptide—A 3T-MRS Study in Healthy Subjects

Zwanzger

Zavorotnyy

Gencheva

et al. 2013

Neuropsychopharmacol

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According to preclinical studies, glutamate has been implicated in the pathogenesis of anxiety. In order to elucidate the role of glutamate in anxiety and panic in humans, brain glutamate þ glutamine (Glx) levels were measured during cholecystokinin-tetrapeptide (CCK-4)-induced panic using magnetic resonance spectroscopy (MRS). Eighteen healthy subjects underwent a CCK-4 challenge. MR spectra were obtained from the anterior cingulate cortex (ACC) using a single voxel point-resolved spectroscopy method and analyzed using LCModel. A combined fitting of Glx was performed. Panic was assessed using the Acute Panic Inventory (API) and Panic Symptom Scale (PSS) scores. Moreover, hypothalamic-pituitary-adrenal axis stimulation was monitored throughout the challenge. There was a significant panic response following CCK-4 as revealed by a marked increase in both the panic scores (API: F(1,17) ¼ 149.41; po0.0001; PSS: F(1,17) ¼ 88.03; po0.0001) and heart rate (HR: F(1,17) ¼ 72.79; po0.0001). MRS measures showed a significant increase of brain Glx/creatine (Glx/Cr) levels peaking at 2-10 min after challenge (F(1,17) ¼ 15.94; p ¼ 0.001). There was also a significant increase in CCK-4-related cortisol release (F(6,11) ¼ 8.68; p ¼ 0.002). Finally, significant positive correlations were found between baseline Glx/Cr and both API max (r ¼ 0.598; p ¼ 0.009) and maximum heart rate (HR max ) during challenge (r ¼ 0.519; p ¼ 0.027). Our results suggest that CCK-4-induced panic is accompanied by a significant glutamate increase in the bilateral ACC. The results add to the hypothesis of a disturbance of the inhibitory-excitatory equilibrium and suggest that apart from static alterations rapid and dynamic neurochemical changes might also be relevant for the neural control of panic attacks.

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“…Of the heritable traits, reward sensitivity and novelty/sensation seeking (Cloninger, 1987;Zuckerman, 1993) have been strongly linked to goaldirected and risk-taking behaviors. These traits are considered significant contributors to the development of drug abuse (Piazza et al, 1989;Belin et al, 2008;Blanchard et al, 2009;Jupp and Dalley, 2014), are found at high levels in gamblers (Janiri et al, 2007) and are positively associated with depressive symptoms and suicidal behavior in adolescents (Ortin et al, 2012). A key component of the neural circuitry shown to be critical for reinforcement learning and goal-directed behavior is the striatonigral/ventral striatomesencephalic (SN/VSM) pathway, which has also been shown to innervate the pallidum (Kupchik et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

A Functional 3′UTR Polymorphism (rs2235749) of Prodynorphin Alters microRNA-365 Binding in Ventral Striatonigral Neurons to Influence Novelty Seeking and Positive Reward Traits

Egervári

Jutras‐Aswad

Landry

et al. 2016

Neuropsychopharmacol

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Genetic factors impact behavioral traits relevant to numerous psychiatric disorders and risk-taking behaviors, and different lines of evidence have indicated that discrete neurobiological systems contribute to such individual differences. In this study, we explored the relationship of genetic variants of the prodynorphin (PDYN) gene, which is enriched in the striatonigral/striatomesencephalic pathway, a key neuronal circuit implicated in positive 'Go' behavioral choice and action. Our multidisciplinary approach revealed that the single nucleotide polymorphism (SNP) rs2235749 (in high linkage disequilibrium with rs910080) modifies striatal PDYN expression via impaired binding of miR-365, a microRNA that targets the PDYN 3′-untranslated region (3′UTR), and is significantly associated to novelty-and reward-related behavioral traits in humans and translational animal models. Carriers of the rs2235749G allele exhibited increased levels of PDYN 3′UTR in vitro and had elevated mRNA expression in the medial nucleus accumbens shell (NAcSh) and caudate nucleus in postmortem human brains. There was an association of rs2235749 with novelty-seeking trait and a strong genotype-dose association with positive reinforcement behavior in control subjects, which differed in cannabis-dependent individuals. Using lentiviral miRZip-365 constructs selectively expressed in Pdyn-neurons of the NAcSh, we demonstrated that the Pdyn-miR365 interaction in the NAcSh directly influences novelty-seeking exploratory behavior and facilitates self-administration of natural reward. Overall, this translational study suggests that genetically determined miR-365-mediated epigenetic regulation of PDYN expression in mesolimbic striatonigral/striatomesencephalic circuits possibly contributes to novelty seeking and positive reinforcement traits.

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The HR/LR model: Further evidence as an animal model of sensation seeking

Cited by 106 publications

References 135 publications

Responses to Novelty and Vulnerability to Cocaine Addiction: Contribution of a Multi-Symptomatic Animal Model

Responses to Novelty and Vulnerability to Cocaine Addiction: Contribution of a Multi-Symptomatic Animal Model

Acute Shift in Glutamate Concentrations Following Experimentally Induced Panic with Cholecystokinin Tetrapeptide—A 3T-MRS Study in Healthy Subjects

A Functional 3′UTR Polymorphism (rs2235749) of Prodynorphin Alters microRNA-365 Binding in Ventral Striatonigral Neurons to Influence Novelty Seeking and Positive Reward Traits

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