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Emilie Jouanjus - One of the best experts on this subject based on the ideXlab platform.

  • Lack of correlation between the activity of the Mesolimbic Dopaminergic System and the rewarding properties of pregabalin in mouse
    Psychopharmacology, 2019
    Co-Authors: Basile Coutens, Lionel Moulédous, Manta Stella, Claire Rampon, Maryse Lapeyre-mestre, Anne Roussin, Bruno Guiard, Emilie Jouanjus
    Abstract:

    Pregabalin is a psychoactive drug indicated in the treatment of epilepsy, neuropathic pain, and generalized anxiety disorders. Pregabalin acts on different neurotransmission Systems by inactivating the alpha2-delta subunit of voltage-gated calcium channels. In light of this pharmacological property, the hypothesis has been raised that pregabalin may regulate the Mesolimbic dopamine pathway and thereby display a potential for misuse or abuse as recently observed in humans. Although some preclinical data support this possibility, the rewarding properties of gabapentinoid are still a matter for debate.

  • Lack of correlation between the activity of the Mesolimbic Dopaminergic System and the rewarding properties of pregabalin in mouse
    Psychopharmacology, 2019
    Co-Authors: Basile Coutens, Lionel Moulédous, Manta Stella, Claire Rampon, Maryse Lapeyre-mestre, Anne Roussin, Bruno Guiard, Emilie Jouanjus
    Abstract:

    Rationale Pregabalin is a psychoactive drug indicated in the treatment of epilepsy, neuropathic pain, and generalized anxiety disorders. Pregabalin acts on different neurotransmission Systems by inactivating the alpha2-delta subunit of voltage-gated calcium channels. In light of this pharmacological property, the hypothesis has been raised that pregabalin may regulate the Mesolimbic dopamine pathway and thereby display a potential for misuse or abuse as recently observed in humans. Although some preclinical data support this possibility, the rewarding properties of gabapentinoid are still a matter for debate. Objective The aim of this work was to evaluate the rewarding properties of pregabalin and to determine its putative mechanism of action in healthy mice. Results Pregabalin alone (60 mg/kg; s.c.) produced a rewarding effect in the conditioned place preference (CPP) test albeit to a lower extent than cocaine (30 mg/kg; s.c.). Interestingly, when assessing locomotor activity in the CPP, the PGB60 group, similarly to the cocaine group, showed an increased locomotor activity. In vivo single unit extracellular recording showed that pregabalin had mixed effects on dopamine (DA) neuronal activity in the ventral tegmental area since it decreased the activity of 50% of neurons and increased 28.5% of them. In contrast, cocaine decreased 75% of VTA DA neuronal activity whereas none of the neurons were activated. Intracerebal microdialysis was then conducted in awake freely mice to determine to what extent such electrophysiological parameters influence the extracellular DA concentrations ([DA]ext) in the nucleus accumbens. Although pregabalin failed to modify this parameter, cocaine produced a robust increase (800%) in [DA]ext. Conclusions Collectively, these electrophysiological and neurochemical experiments suggest that the rewarding properties of pregabalin result from a different mode of action than that observed with cocaine. Further experiments are warranted to determine whether such undesirable effects can be potentiated under pathological conditions such as neuropathic pain, mood disorders, or addiction and to identify the key neurotransmitter System involved.

  • Lack of correlation between the activity of the Mesolimbic Dopaminergic System and the rewarding properties of pregabalin in mouse.
    Psychopharmacology, 2019
    Co-Authors: Basile Coutens, Lionel Moulédous, Manta Stella, Claire Rampon, Maryse Lapeyre-mestre, Anne Roussin, Bruno Guiard, Emilie Jouanjus
    Abstract:

    Pregabalin is a psychoactive drug indicated in the treatment of epilepsy, neuropathic pain, and generalized anxiety disorders. Pregabalin acts on different neurotransmission Systems by inactivating the alpha2-delta subunit of voltage-gated calcium channels. In light of this pharmacological property, the hypothesis has been raised that pregabalin may regulate the Mesolimbic dopamine pathway and thereby display a potential for misuse or abuse as recently observed in humans. Although some preclinical data support this possibility, the rewarding properties of gabapentinoid are still a matter for debate. The aim of this work was to evaluate the rewarding properties of pregabalin and to determine its putative mechanism of action in healthy mice. Pregabalin alone (60 mg/kg; s.c.) produced a rewarding effect in the conditioned place preference (CPP) test albeit to a lower extent than cocaine (30 mg/kg; s.c.). Interestingly, when assessing locomotor activity in the CPP, the PGB60 group, similarly to the cocaine group, showed an increased locomotor activity. In vivo single unit extracellular recording showed that pregabalin had mixed effects on dopamine (DA) neuronal activity in the ventral tegmental area since it decreased the activity of 50% of neurons and increased 28.5% of them. In contrast, cocaine decreased 75% of VTA DA neuronal activity whereas none of the neurons were activated. Intracerebal microdialysis was then conducted in awake freely mice to determine to what extent such electrophysiological parameters influence the extracellular DA concentrations ([DA]ext) in the nucleus accumbens. Although pregabalin failed to modify this parameter, cocaine produced a robust increase (800%) in [DA]ext. Collectively, these electrophysiological and neurochemical experiments suggest that the rewarding properties of pregabalin result from a different mode of action than that observed with cocaine. Further experiments are warranted to determine whether such undesirable effects can be potentiated under pathological conditions such as neuropathic pain, mood disorders, or addiction and to identify the key neurotransmitter System involved.

Basile Coutens - One of the best experts on this subject based on the ideXlab platform.

  • Lack of correlation between the activity of the Mesolimbic Dopaminergic System and the rewarding properties of pregabalin in mouse
    Psychopharmacology, 2019
    Co-Authors: Basile Coutens, Lionel Moulédous, Manta Stella, Claire Rampon, Maryse Lapeyre-mestre, Anne Roussin, Bruno Guiard, Emilie Jouanjus
    Abstract:

    Pregabalin is a psychoactive drug indicated in the treatment of epilepsy, neuropathic pain, and generalized anxiety disorders. Pregabalin acts on different neurotransmission Systems by inactivating the alpha2-delta subunit of voltage-gated calcium channels. In light of this pharmacological property, the hypothesis has been raised that pregabalin may regulate the Mesolimbic dopamine pathway and thereby display a potential for misuse or abuse as recently observed in humans. Although some preclinical data support this possibility, the rewarding properties of gabapentinoid are still a matter for debate.

  • Lack of correlation between the activity of the Mesolimbic Dopaminergic System and the rewarding properties of pregabalin in mouse
    Psychopharmacology, 2019
    Co-Authors: Basile Coutens, Lionel Moulédous, Manta Stella, Claire Rampon, Maryse Lapeyre-mestre, Anne Roussin, Bruno Guiard, Emilie Jouanjus
    Abstract:

    Rationale Pregabalin is a psychoactive drug indicated in the treatment of epilepsy, neuropathic pain, and generalized anxiety disorders. Pregabalin acts on different neurotransmission Systems by inactivating the alpha2-delta subunit of voltage-gated calcium channels. In light of this pharmacological property, the hypothesis has been raised that pregabalin may regulate the Mesolimbic dopamine pathway and thereby display a potential for misuse or abuse as recently observed in humans. Although some preclinical data support this possibility, the rewarding properties of gabapentinoid are still a matter for debate. Objective The aim of this work was to evaluate the rewarding properties of pregabalin and to determine its putative mechanism of action in healthy mice. Results Pregabalin alone (60 mg/kg; s.c.) produced a rewarding effect in the conditioned place preference (CPP) test albeit to a lower extent than cocaine (30 mg/kg; s.c.). Interestingly, when assessing locomotor activity in the CPP, the PGB60 group, similarly to the cocaine group, showed an increased locomotor activity. In vivo single unit extracellular recording showed that pregabalin had mixed effects on dopamine (DA) neuronal activity in the ventral tegmental area since it decreased the activity of 50% of neurons and increased 28.5% of them. In contrast, cocaine decreased 75% of VTA DA neuronal activity whereas none of the neurons were activated. Intracerebal microdialysis was then conducted in awake freely mice to determine to what extent such electrophysiological parameters influence the extracellular DA concentrations ([DA]ext) in the nucleus accumbens. Although pregabalin failed to modify this parameter, cocaine produced a robust increase (800%) in [DA]ext. Conclusions Collectively, these electrophysiological and neurochemical experiments suggest that the rewarding properties of pregabalin result from a different mode of action than that observed with cocaine. Further experiments are warranted to determine whether such undesirable effects can be potentiated under pathological conditions such as neuropathic pain, mood disorders, or addiction and to identify the key neurotransmitter System involved.

  • Lack of correlation between the activity of the Mesolimbic Dopaminergic System and the rewarding properties of pregabalin in mouse.
    Psychopharmacology, 2019
    Co-Authors: Basile Coutens, Lionel Moulédous, Manta Stella, Claire Rampon, Maryse Lapeyre-mestre, Anne Roussin, Bruno Guiard, Emilie Jouanjus
    Abstract:

    Pregabalin is a psychoactive drug indicated in the treatment of epilepsy, neuropathic pain, and generalized anxiety disorders. Pregabalin acts on different neurotransmission Systems by inactivating the alpha2-delta subunit of voltage-gated calcium channels. In light of this pharmacological property, the hypothesis has been raised that pregabalin may regulate the Mesolimbic dopamine pathway and thereby display a potential for misuse or abuse as recently observed in humans. Although some preclinical data support this possibility, the rewarding properties of gabapentinoid are still a matter for debate. The aim of this work was to evaluate the rewarding properties of pregabalin and to determine its putative mechanism of action in healthy mice. Pregabalin alone (60 mg/kg; s.c.) produced a rewarding effect in the conditioned place preference (CPP) test albeit to a lower extent than cocaine (30 mg/kg; s.c.). Interestingly, when assessing locomotor activity in the CPP, the PGB60 group, similarly to the cocaine group, showed an increased locomotor activity. In vivo single unit extracellular recording showed that pregabalin had mixed effects on dopamine (DA) neuronal activity in the ventral tegmental area since it decreased the activity of 50% of neurons and increased 28.5% of them. In contrast, cocaine decreased 75% of VTA DA neuronal activity whereas none of the neurons were activated. Intracerebal microdialysis was then conducted in awake freely mice to determine to what extent such electrophysiological parameters influence the extracellular DA concentrations ([DA]ext) in the nucleus accumbens. Although pregabalin failed to modify this parameter, cocaine produced a robust increase (800%) in [DA]ext. Collectively, these electrophysiological and neurochemical experiments suggest that the rewarding properties of pregabalin result from a different mode of action than that observed with cocaine. Further experiments are warranted to determine whether such undesirable effects can be potentiated under pathological conditions such as neuropathic pain, mood disorders, or addiction and to identify the key neurotransmitter System involved.

Martin Reuter - One of the best experts on this subject based on the ideXlab platform.

  • Oxytocinergic modulation of brain activation to cues related to reproduction and attachment: Differences and commonalities during the perception of erotic and fearful social scenes.
    International journal of psychophysiology : official journal of the International Organization of Psychophysiology, 2018
    Co-Authors: Carina Sauer, Christian Montag, Martin Reuter, Peter Kirsch
    Abstract:

    Abstract In animal research, the neuropeptide oxytocin (OT) has been known for its role in reproduction and attachment for a longer time. There is strong evidence for an involvement of the Mesolimbic Dopaminergic System for these effects of OT. In contrast, human research rather concentrated on more human concepts of social cognition and behavior (e.g. trust or processing of fearful faces) and mainly focused on the amygdala as the main neurobiological substrate. To extend this view, we wanted to gain more insight into the neurobiological effects of OT in the context of reproduction and attachment in humans and compare these effects to its well-known effects on fear processing. In a double-blind placebo-controlled fMRI study, we investigated 55 healthy young men using intranasal OT administration. During fMRI, participants saw attachment-related erotic scenes and fearful social scenes. Over all participants, OT had a differential effect on processing of erotic and fearful scenes. While OT administration led to a relative increase of neural activation in Mesolimbic structures during processing of erotic stimuli, it decreased amygdala activation for fearful stimuli. On the individual level, we observed significant positive correlations between OT induced activation changes across different brain regions and under different stimulus conditions. Our findings extend the already existing animal literature and provide evidence for a similar involvement of the Mesolimbic Dopaminergic System for OT effects in the context of reproduction and attachment in humans.

  • Epistasis of the DRD2/ANKK1 Taq Ia and the BDNF Val66Met Polymorphism Impacts Novelty Seeking and Harm Avoidance
    Neuropsychopharmacology, 2010
    Co-Authors: Christian Montag, Sebastian Markett, Ulrike Basten, Christine Stelzel, Christian Fiebach, Turhan Canli, Martin Reuter
    Abstract:

    Mounting evidence from animal studies show that the Mesolimbic Dopaminergic pathways are modulated by the brain-derived neurotrophic factor (BDNF). This study investigates in N =768 healthy Caucasian participants the influence of two prominent functional single-nucleotide polymorphisms (SNPs) on the BDNF gene (BDNF Val66Met SNP) and the ankyrin repeat and kinase domain containing 1 (ANKK1) gene (DRD2 Taq Ia/ANKK1 SNP) on the personality traits of Novelty Seeking and Harm Avoidance, which are mediated, in part, through Dopaminergic Mesolimbic circuitry. Carriers of the 66Met+/A1+ variant scored lowest on Novelty Seeking and highest on Harm Avoidance, compared to all other genotype groups. These participants are characterized by a relatively low D_2 receptor density in the striatum and an impaired activity-dependent secretion of BDNF. This is one of the first genetic association studies to show a modulatory role for BDNF genetic variation on genetically mediated differences in the Mesolimbic Dopaminergic System in the context of human personality.

  • Epistasis of the DRD2/ANKK1 Taq Ia and the BDNF Val66Met polymorphism impacts Novelty Seeking and Harm Avoidance
    Neuropsychopharmacology, 2010
    Co-Authors: Christian Montag, Sebastian Markett, Ulrike Basten, Christine Stelzel, Christian Fiebach, Turhan Canli, Martin Reuter
    Abstract:

    Mounting evidence from animal studies show that the Mesolimbic Dopaminergic pathways are modulated by the brain derived neurotrophic factor (BDNF). This study investigates in N = 768 healthy Caucasian participants the influence of two prominent functional single nucleotide polymorphisms (SNPs) on the BDNF gene (BDNF Val66Met SNP) and the ANKK1 gene (DRD2 Taq Ia / ANKK1 SNP) on the personality traits of Novelty Seeking and Harm Avoidance, which are mediated, in part, through Dopaminergic Mesolimbic circuitry. Carriers of the 66Met+/A1+ variant scored lowest on Novelty Seeking and highest on Harm Avoidance, compared to all other genotype groups. These participants are characterized by a relatively low D2 receptor density in the striatum and an impaired activity-dependent secretion of BDNF. This is one of the first genetic association studies to demonstrate a modulatory role for BDNF genetic variation on genetically mediated differences in the Mesolimbic Dopaminergic System in the context of human personality

Antonio Argiolas - One of the best experts on this subject based on the ideXlab platform.

  • dopamine noradrenaline and differences in sexual behavior between roman high and low avoidance male rats a microdialysis study in the medial prefrontal cortex
    Frontiers in Behavioral Neuroscience, 2017
    Co-Authors: Fabrizio Sanna, Jessica Bratzu, Maria Antonietta Piludu, Maria Giuseppa Corda, Maria Rosaria Melis, Osvaldo Giorgi, Antonio Argiolas
    Abstract:

    Roman High- (RHA) and Low-Avoidance (RLA) outbred rats, which differ for a respectively rapid vs. poor acquisition of the active avoidance response in the shuttle-box, display differences in sexual activity when put in the presence of a sexually receptive female rat. Indeed RHA rats show higher levels of sexual motivation and copulatory performance than RLA rats, which persist also after repeated sexual activity. These differences have been correlated to a higher tone of the Mesolimbic Dopaminergic System of RHA rats vs. RLA rats, revealed by the higher increase of dopamine found in the dialysate obtained from the nucleus accumbens of RHA than RLA rats during sexual activity. This work shows that extracellular dopamine and noradrenaline also, increase in the dialysate from the medial prefrontal cortex of male RHA and RLA rats put in the presence of an inaccessible female rat and more markedly during direct sexual interaction. Such increases in dopamine (and its main metabolite DOPAC) and noradrenaline were found in both sexually naive and experienced animals, but they were higher i) in RHA than in RLA rats and ii) in sexually experienced RHA and RLA rats than in their naive counterparts. Finally, the differences in dopamine and noradrenaline in the medial prefrontal cortex occurred concomitantly to those in sexual activity, as RHA rats displayed higher levels of sexual motivation and copulatory performance than RLA rats in both the sexually naive and experienced conditions. These results suggest that a higher Dopaminergic tone also occurs in the medial prefrontal cortex, together with an increased noradrenergic tone, which may be involved in the different copulatory patterns found in RHA and RLA rats, as suggested for the Mesolimbic Dopaminergic System.

Marc Fantino - One of the best experts on this subject based on the ideXlab platform.

  • Mesolimbic Dopaminergic System activity as a function of food reward: A microdialysis study
    Pharmacology Biochemistry and Behavior, 1996
    Co-Authors: Patricia Martel, Marc Fantino
    Abstract:

    Abstract The Mesolimbic Dopaminergic System (MDS) has been shown to be implicated in feeding behaviors. The present experiment was conducted to examine the effects of the sensory properties of food ingested on MDS activity. Microdialysis coupled to high-performance liquid chromatography with electrochemical detection was employed to measure the extracellular levels of dopamine (DA) and its main metabolites (DOPAC and HVA) in the nucleus accumbens of freely moving rats. During microdialysis sessions rats had access or not to powdered foods varying in palatability: short cakes as highly palatable (HP) food and regular chow as low palatable (LP) food. In the absence of food, there were no alterations in extracellular levels of DA, DOPAC, and HVA. During feeding, DA rose significantly with a greater rise for the HP than the LP food. Levels of DOPAC and HVA only reached significance with the HP food. The results indicate that the MDS is activated on ingestion of food, and suggest that MDS activity is related to the rewarding properties of foods.

  • Influence of the amount of food ingested on Mesolimbic Dopaminergic System activity: A microdialysis study
    Pharmacology biochemistry and behavior, 1996
    Co-Authors: Patricia Martel, Marc Fantino
    Abstract:

    Abstract The Mesolimbic Dopaminergic System (MDS) has been shown to be activated by ingestive behaviors, and it has been suggested that this activation may be related to the rewarding properties of foods. Because rats eat more when given a more palatable diet, this study was undertaken to determine the relationship between the amount of food ingested and DA release in the nucleus accumbens of freely moving rats. The extracellular levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured by high-performance liquid chromatography with electrochemical detection on microdialysis samples from the nucleus accumbens. Each rat underwent three microdialysis sessions that differed in feeding conditions: on the first day they had access to a highly palatable diet (short cakes) ad lib; on the second day they were given half the amount consumed on the previous day of the same food; and on the third day they were deprived of food. In the absence of food, there were no significant alterations in extracellular levels of DA, DOPAC, and HVA. During feeding, levels of DA and its two metabolites rose. DA release in the nucleus accumbens was related to the amount of food ingested. As the amount ingested is a component of the reinforcement associated with food intake, this result is consistent with a direct relationship between MDS activity and food reward.