The Experts below are selected from a list of 279 Experts worldwide ranked by ideXlab platform

Annenoel Samaha - One of the best experts on this subject based on the ideXlab platform.

  • where and how does d amphetamine act to reveal antipsychotic induced dopamine supersensitivity in rats
    bioRxiv, 2020
    Co-Authors: Alice Servonnet, Florence Allain, A Gravelchouinard, Giovanni Hernandez, Bourdeau C Caporuscio, M Legrix, Daniel Levesque, Pierrepaul Rompre, Annenoel Samaha
    Abstract:

    Antipsychotic treatment can produce a dopamine supersensitive state. In both schizophrenia patients and rodents, this is linked to antipsychotic treatment failure. In rodents, dopamine supersensitivity is often confirmed by an exaggerated behavioural response to the indirect monoamine agonist, d-amphetamine, after discontinuation of antipsychotic treatment. Here we investigated where and how d-amphetamine acts to trigger behavioural expression of dopamine supersensitivity, as this could uncover pathophysiological mechanisms underlying this supersensitivity. First, we examined the contributions of a central increase in dopamine/monoamine Activity. Haloperidol-treated rats showed a potentiated Psychomotor response to systemic d-amphetamine, confirming dopamine supersensitivity. However, they showed a normal Psychomotor response to an increase in ventral midbrain dopamine impulse flow or to intracerebroventricular injection of d-amphetamine. This suggests that d-amphetamines peripheral effects are required for a supersensitive response. Second, we determined the specific contributions of dopamine neurotransmission. The D2 agonist quinpirole, but not the D1 agonist SKF38393 or the dopamine reuptake blocker GBR12783 produced a supersensitive Psychomotor response in haloperidol-treated rats. In these rats, the D1 antagonist SCH39166 decreased d-amphetamine-induced Psychomotor Activity, whereas the D2 antagonist sulpiride enhanced it. Thus, when d-amphetamine triggers a supersensitive response, this involves both D1- and D2-mediated transmission. Finally, we measured d-amphetamine-induced changes in D1- and D2-mediated intracellular signalling pathways in the striatum. In haloperidol-treated rats, a supersensitive response to d-amphetamine was linked to enhanced GSK3{beta} Activity and suppressed ERK1/2 Activity in the nucleus accumbens, suggesting increased D2-mediated signalling. These findings provide new insights into the neurobiology of antipsychotic-evoked dopamine supersensitivity.

  • varying the rate of intravenous cocaine infusion influences the temporal dynamics of both drug and dopamine concentrations in the striatum
    European Journal of Neuroscience, 2019
    Co-Authors: Ellieanna Minogianis, Waqqas M Shams, Omar S Mabrouk, Jennymarie T Wong, Wayne G Brake, Robert T Kennedy, Patrick Du Souich, Annenoel Samaha
    Abstract:

    The faster drugs of abuse reach the brain, the greater is the risk of addiction. Even small differences in the rate of drug delivery can influence outcome. Infusing cocaine intravenously over 5 vs. 90-100 s promotes sensitization to the Psychomotor and incentive motivational effects of the drug and preferentially recruits mesocorticolimbic regions. It remains unclear whether these effects are due to differences in how fast and/or how much drug reaches the brain. Here, we predicted that varying the rate of intravenous cocaine infusion between 5 and 90 s produces different rates of rise of brain drug concentrations, while producing similar peak concentrations. Freely moving male Wistar rats received acute intravenous cocaine infusions (2.0 mg/kg/infusion) over 5, 45 and 90 s. We measured cocaine concentrations in the dorsal striatum using rapid-sampling microdialysis (1 sample/min) and high-performance liquid chromatography-tandem mass spectrometry. We also measured extracellular concentrations of dopamine and other neurochemicals. Regardless of infusion rate, acute cocaine did not change concentrations of non-dopaminergic neurochemicals. Infusion rate did not significantly influence peak concentrations of cocaine or dopamine, but concentrations increased faster following 5-s infusions. We also assessed Psychomotor Activity as a function of cocaine infusion rate. Infusion rate did not significantly influence total locomotion, but locomotion increased earlier following 5-s infusions. Thus, small differences in the rate of cocaine delivery influence both the rate of rise of drug and dopamine concentrations, and Psychomotor Activity. A faster rate of rise of drug and dopamine concentrations might be an important issue in making rapidly delivered cocaine more addictive.

  • 5 ht2 receptors modulate the expression of antipsychotic induced dopamine supersensitivity
    European Neuropsychopharmacology, 2015
    Co-Authors: Alexandra Charron, Alice Servonnet, Cynthia El Hage, Annenoel Samaha
    Abstract:

    Abstract Antipsychotic treatment can produce supersensitivity to dopamine receptor stimulation. This compromises the efficacy of ongoing treatment and increases the risk of relapse to psychosis upon treatment cessation. Serotonin 5-HT 2 receptors modulate dopamine function and thereby influence dopamine-dependent responses. Here we evaluated the hypothesis that 5-HT 2 receptors modulate the behavioural expression of antipsychotic-induced dopamine supersensitivity. To this end, we first treated rats with the antipsychotic haloperidol using a clinically relevant treatment regimen. We then assessed the effects of a 5-HT 2 receptor antagonist (ritanserin; 0.01 and 0.1 mg/kg) and of a 5-HT 2A receptor antagonist (MDL100,907; 0.025–0.1 mg/kg) on amphetamine-induced Psychomotor Activity. Antipsychotic-treated rats showed increased amphetamine-induced locomotion relative to antipsychotic-naive rats, indicating a dopamine supersensitive state. At the highest dose tested (0.1 mg/kg for both antagonists), both ritanserin and MDL100,907 suppressed amphetamine-induced locomotion in antipsychotic-treated rats, while having no effect on this behaviour in control rats. In parallel, antipsychotic treatment decreased 5-HT 2A receptor density in the prelimbic cortex and nucleus accumbens core and increased 5-HT 2A receptor density in the caudate-putamen. Thus, activation of either 5-HT 2 receptors or of 5-HT 2A receptors selectively is required for the full expression of antipsychotic-induced dopamine supersensitivity. In addition, antipsychotic-induced dopamine supersensitivity enhances the ability of 5-HT 2 /5-HT 2A receptors to modulate dopamine-dependent behaviours. These effects are potentially linked to changes in 5-HT 2A receptor density in the prefrontal cortex and the striatum. These observations raise the possibility that blockade of 5-HT 2A receptors might overcome some of the behavioural manifestations of antipsychotic-induced dopamine supersensitivity.

Kouhei Matsuda - One of the best experts on this subject based on the ideXlab platform.

  • orexin a enhances locomotor Activity and induces anxiogenic like action in the goldfish carassius auratus
    Hormones and Behavior, 2014
    Co-Authors: Tomoya Nakamachi, Haruki Shibata, Atsushi Sakashita, Naoto Iinuma, Kohei Wada, Norifumi Konno, Kouhei Matsuda
    Abstract:

    Abstract Orexin acts as an orexigenic factor for the regulation of appetite and rhythmicity in rodents. In goldfish, intracerebroventricular (ICV) administration of orexin A has been shown to affect not only food intake, but also locomotor Activity. However, as there is still no information regarding the effect of orexin A on emotional behavior in goldfish, we investigated the effect of orexin A on Psychomotor Activity in this species. Intracerebroventricular administration of synthetic orexin A at 2 and 4 pmol/g body weight (BW) enhanced locomotor Activity, and this enhancement by orexin A at 4 pmol/g BW was attenuated by treatment with the orexin receptor 1 antagonist, SB334867, at 10 pmol/g BW. Since intact goldfish prefer a black to a white background area, or the lower to the upper area of a tank, we used two types of preference tests (black/white and upper/lower tests) for measuring anxiety-like behavior in goldfish. Intracerebroventricular administration of orexin A at 4 pmol/g BW shortened the time spent in the white background area, and increased the time taken to move from the lower to the upper area. This action of orexin A mimicked that of the central-type benzodiazepine receptor inverse agonist, FG-7142 (an anxiogenic agent), at 4 pmol/g BW. The anxiogenic-like effect of orexin A was abolished by treatment with SB334867 at 10 pmol/g BW. These results indicate that orexin A potently affects Psychomotor Activity in goldfish.

  • ovine corticotropin releasing hormone ocrh exerts an anxiogenic like action in the goldfish carassius auratus
    General and Comparative Endocrinology, 2013
    Co-Authors: Kouhei Matsuda, Haruki Shibata, Atsushi Sakashita, Yasunari Hagiwara, Kohei Wada
    Abstract:

    Abstract Corticotropin-releasing hormone (CRH) is a member of the hypothalamic neuropeptide family that includes urocortins, urotensin I and sauvagine in vertebrates. CRH and urocortin act as anorexigenic factors for satiety regulation in rodents. In a goldfish model, intracerebroventricular (ICV) administration of ovine CRH (oCRH) affects not only food intake, but also locomotor Activity. However, there is no information regarding the psychophysiological roles of CRH in goldfish. Therefore, we investigated the effect of oCRH on Psychomotor Activity in this species. ICV administration of synthetic oCRH at 20 pmol/g body weight (BW) enhanced locomotor Activity. Since intact goldfish prefer the lower to the upper area of a tank, we developed a method for measuring the time taken for fish to move from the lower to the upper area. ICV administration of oCRH at 20 pmol/g BW and the central-type benzodiazepine receptor inverse agonist FG-7142 (an anxiogenic agent) at 1–4 pmol/g BW both increased the time taken to move from the lower to the upper area. This anxiogenic-like effect of oCRH was abolished by the CRH receptor antagonist α-helical CRH (9–41) (100 pmol/g BW). These results indicate that CRH can potently affect locomotor and Psychomotor activities in goldfish.

  • neuroendocrine control of feeding behavior and Psychomotor Activity by pituitary adenylate cyclase activating polypeptide pacap in vertebrates
    Obesity Research & Clinical Practice, 2013
    Co-Authors: Kouhei Matsuda, Morio Azuma, Keisuke Maruyama, Seiji Shioda
    Abstract:

    Food intake is a fundamental for animals to surviving and keeping offspring. The hypothalamic region of the brain and the brain stem in vertebrates are a center that plays an important role in the control of feeding and its related behaviors including locomotor and Psychomotor activities. Pituitary adenylate cyclase-activating polypeptide (PACAP) has firstly been identified as a hypophysiotropic hormone involved in adenohypophyseal hormone release, and subsequently has been considered as a neuropeptide exerting multifunctional roles in the central and peripheral nervous systems and several tissues in vertebrates. For example, PACAP is involved in the neuroendocrine control of food intake and acts as an anorexigenic peptide to regulate satiety. Recent works on animal models such as rodents and goldfish which are both excellent animal models for investigating the neuroendocrinological roles of PACAP have been extensively examined and considerable information has been accumulated. In addition, psychophysiological effects of PACAP on emotional behavior have recently been found. Therefore, this review article provides an overview of the neuroendocrine regulation of feeding behavior and psyphysiological Activity by PACAP in vertebrates.

  • neuroendocrine control of feeding behavior and Psychomotor Activity by neuropeptidey in fish
    Neuropeptides, 2012
    Co-Authors: Kouhei Matsuda, Atsushi Sakashita, Eri Yokobori, Morio Azuma
    Abstract:

    Neuropeptide Y (NPY) is a neuropeptide distributed widely among vertebrates. In mammals, NPY and its related peptides such as pancreatic polypeptide and peptide YY (PYY) are distributed throughout the brain and gastrointestinal tissues, and are centrally involved in many physiological functions such as the regulation of food intake, locomotion and Psychomotor activities through their receptors. With regard to non-mammalian vertebrates, there has also been intensive study aimed at the identification and functional characterization of NPY, PYY and their receptors, and recent investigations of the role of NPY have revealed that it exerts several behavioral effects in goldfish and zebrafish. Both of these species are excellent teleost fish models, in which it has been demonstrated that NPY increases food consumption as an orexigenic factor and reduces locomotor Activity, as is the case in mammals. This paper reviews current knowledge of NPY derived from studies of teleost fish, as representative non-mammals, focusing particularly on the role of the NPY system, and examines its significance from a comparative viewpoint.

  • the effects of ghrelin on energy balance and Psychomotor Activity in a goldfish model an overview
    International Journal of Peptides, 2011
    Co-Authors: Ki Sung Kang, Satowa Yahashi, Kouhei Matsuda
    Abstract:

    The goldfish (Carassius auratus) has a number of merits as a laboratory animal, and we have extensively identified the mechanisms by which ghrelin regulates food intake in this species. For the first time, we have purified and characterized 11 molecular variants of ghrelin that are present in goldfish intestine and shown that 17-residue ghrelin, the predominant form with n-octanoyl modification, is biologically active and implicated in the regulation of food intake as an endogenous orexigenic factor. Ghrelin and its receptor system are present not only in peripheral tissues such as stomach and intestine, but also in the central nervous system. Recent studies have also revealed that a number of neuropeptides are widely distributed in the brain in key areas of emotional regulation, and their role as modulators of behavioral states is being increasingly recognized. Interestingly, administration of ghrelin induces an orexigenic effect and also modifies locomotor Activity, suggesting the involvement of ghrelin in feeding control and regulation of energy balance. Information derived from studies of ghrelin has been increasing, and important results have been obtained from both fish and mammals. Here, we present an overview of the effects of ghrelin on energy balance and Psychomotor Activity in the goldfish as an animal model. The available data provide an insight into evolutionary background of ghrelin's multiple actions on energy homeostasis in vertebrates.

Maria Faurholtjepsen - One of the best experts on this subject based on the ideXlab platform.

  • differences in Psychomotor Activity and heart rate variability in patients with newly diagnosed bipolar disorder unaffected relatives and healthy individuals
    Journal of Affective Disorders, 2020
    Co-Authors: Josefine Freyberg, Lars Vedel Kessing, Soren Brage, Maria Faurholtjepsen
    Abstract:

    Abstract Background Heart rate variability (HRV) and Psychomotor Activity have been found reduced in bipolar disorder (BD) but has never been investigated in newly diagnosed BD and unaffected relatives. The present study aimed to compare HRV and Psychomotor Activity between newly diagnosed patients with BD, their unaffected first-degree relatives (UR), and healthy control individuals (HC). Methods 20 newly diagnosed patients with BD, 20 of their UR, and 20 age- and sex-matched HC were included. Measurements of HRV for five minutes and heart rate and acceleration for seven days were conducted. Activity energy expenditure (AEE) was derived from the latter. Linear mixed effect regression models were conducted to compare the three groups. Results HRV did not differ in any measure between the three groups of participants. Similarly, AEE (kJ/day/kg) did not differ between the three groups in neither daily means (BD: 63.6, UR: 64.1, HC: 62.1) nor when divided into quarter-daily intervals. Limitations The relatively small size of the study may affect the validity of the results. Conclusion Patients with newly diagnosed BD and UR do not present with decreased HRV or AEE. These results contrast prior findings from BD patients with more advanced stages of the disorder, suggesting that these outcomes progress with illness duration.

  • state related differences in the level of Psychomotor Activity in patients with bipolar disorder continuous heart rate and movement monitoring
    Psychiatry Research-neuroimaging, 2016
    Co-Authors: Maria Faurholtjepsen, Soren Brage, Maj Vinberg, Lars Vedel Kessing
    Abstract:

    Measuring changes in Psychomotor Activity is a potential tool in the monitoring of the course of affective states in bipolar disorder. Previous studies have been cross-sectional and only some have used objective measures. The aim was to investigate state-related differences in objectively-measured Psychomotor Activity in bipolar disorder. During a 12 weeks study, repeated measurements of heart rate and movement monitoring over several days were collected during different affective states from 19 outpatients with bipolar disorder. Outcomes included Activity energy expenditure (AEE) and trunk acceleration (ACC). Symptoms were clinically assessed using Hamilton Depression Rating Scale (HDRS-17) and Young Mania Rating Scale (YMRS). Compared to patients in a euthymic state, patients in a manic state had significantly higher AEE. Compared to patients in a depressive state, patients in a manic state had significantly higher ACC and AEE. There was a significant diurnal variation in ACC and AEE between affective states. Finally, there was a significant correlation between the severity of manic symptoms and ACC and AEE, respectively. This first study measuring Psychomotor Activity during different affective states using a combined heart rate and movement sensor supports that Psychomotor Activity is a core symptom in bipolar disorder that is altered during affective states.

  • electronic monitoring of Psychomotor Activity as a supplementary objective measure of depression severity
    Nordic Journal of Psychiatry, 2015
    Co-Authors: Maria Faurholtjepsen, Soren Brage, Maj Vinberg, Ellen Margrethe Christensen, Ulla Knorr, Hans Morch Jensen, Lars Vedel Kessing
    Abstract:

    AbstractBackground: Rating scales used to assess the severity of depression e.g. the Hamilton Depression Rating Scale 17-item (HDRS-17) partly rely on the patient's subjective experience and reporting. Such subjective measures tend to have low reliability and adding objective measures to complement the assessment of depression severity would be a major step forward. Aims: To investigate correlations between electronic monitoring of Psychomotor Activity and severity of depression according to HDRS-17. Methods: A total of 36 patients with unipolar disorder (n = 18) or bipolar disorder (n = 18) and 31 healthy control persons aged 18–60 years were included. Psychomotor Activity was measured using a combined heart rate and movement sensor device (Actiheart) for 3 consecutive days, 24 h a day. Results: We found that sleeping heart rate (beats/min) correlated with HDRS-17 in both patients with unipolar disorder and bipolar disorder (unadjusted model: B = 0.46, 95% CI 0.037–0.89, P = 0.034). In contrast, correlat...

  • differences in Psychomotor Activity in patients suffering from unipolar and bipolar affective disorder in the remitted or mild moderate depressive state
    Journal of Affective Disorders, 2012
    Co-Authors: Maria Faurholtjepsen, Soren Brage, Maj Vinberg, Ellen Margrethe Christensen, Ulla Knorr, Hans Morch Jensen, Lars Vedel Kessing
    Abstract:

    Abstract Background Abnormalities in Psychomotor Activity are a central and essential feature of affective disorder. Studies measuring differences in Psychomotor Activity between unipolar and bipolar disorder show divergent results and none have used a combined heart rate and movement monitor for measuring Activity during free-living conditions. Objective To compare objectively measured Psychomotor Activity in patients with unipolar and bipolar disorder in a remitted or mild/moderate depressive state. Further, both groups were compared to a healthy control group. Methods A cross-sectional study of outpatients suffering from unipolar (n = 20) and bipolar (n = 18) disorder and healthy controls (n = 31), aged 18–60 years. For three consecutive days a combined acceleration (m/s2) and heart rate (beats per minute) monitoring was used in conjunction with a step test to estimate Activity energy expenditure (J/min/kg) as measures of Psychomotor Activity and physical fitness. Results Overall score on Hamilton-17 items ranged between 0 and 22. Patients had higher sleeping heart rate (p  Conclusions Electronic monitoring of Psychomotor Activity may be a promising additional tool in the distinction between unipolar and bipolar affective disorder when patients present in a remitted or depressive state.

Lars Vedel Kessing - One of the best experts on this subject based on the ideXlab platform.

  • differences in Psychomotor Activity and heart rate variability in patients with newly diagnosed bipolar disorder unaffected relatives and healthy individuals
    Journal of Affective Disorders, 2020
    Co-Authors: Josefine Freyberg, Lars Vedel Kessing, Soren Brage, Maria Faurholtjepsen
    Abstract:

    Abstract Background Heart rate variability (HRV) and Psychomotor Activity have been found reduced in bipolar disorder (BD) but has never been investigated in newly diagnosed BD and unaffected relatives. The present study aimed to compare HRV and Psychomotor Activity between newly diagnosed patients with BD, their unaffected first-degree relatives (UR), and healthy control individuals (HC). Methods 20 newly diagnosed patients with BD, 20 of their UR, and 20 age- and sex-matched HC were included. Measurements of HRV for five minutes and heart rate and acceleration for seven days were conducted. Activity energy expenditure (AEE) was derived from the latter. Linear mixed effect regression models were conducted to compare the three groups. Results HRV did not differ in any measure between the three groups of participants. Similarly, AEE (kJ/day/kg) did not differ between the three groups in neither daily means (BD: 63.6, UR: 64.1, HC: 62.1) nor when divided into quarter-daily intervals. Limitations The relatively small size of the study may affect the validity of the results. Conclusion Patients with newly diagnosed BD and UR do not present with decreased HRV or AEE. These results contrast prior findings from BD patients with more advanced stages of the disorder, suggesting that these outcomes progress with illness duration.

  • state related differences in the level of Psychomotor Activity in patients with bipolar disorder continuous heart rate and movement monitoring
    Psychiatry Research-neuroimaging, 2016
    Co-Authors: Maria Faurholtjepsen, Soren Brage, Maj Vinberg, Lars Vedel Kessing
    Abstract:

    Measuring changes in Psychomotor Activity is a potential tool in the monitoring of the course of affective states in bipolar disorder. Previous studies have been cross-sectional and only some have used objective measures. The aim was to investigate state-related differences in objectively-measured Psychomotor Activity in bipolar disorder. During a 12 weeks study, repeated measurements of heart rate and movement monitoring over several days were collected during different affective states from 19 outpatients with bipolar disorder. Outcomes included Activity energy expenditure (AEE) and trunk acceleration (ACC). Symptoms were clinically assessed using Hamilton Depression Rating Scale (HDRS-17) and Young Mania Rating Scale (YMRS). Compared to patients in a euthymic state, patients in a manic state had significantly higher AEE. Compared to patients in a depressive state, patients in a manic state had significantly higher ACC and AEE. There was a significant diurnal variation in ACC and AEE between affective states. Finally, there was a significant correlation between the severity of manic symptoms and ACC and AEE, respectively. This first study measuring Psychomotor Activity during different affective states using a combined heart rate and movement sensor supports that Psychomotor Activity is a core symptom in bipolar disorder that is altered during affective states.

  • electronic monitoring of Psychomotor Activity as a supplementary objective measure of depression severity
    Nordic Journal of Psychiatry, 2015
    Co-Authors: Maria Faurholtjepsen, Soren Brage, Maj Vinberg, Ellen Margrethe Christensen, Ulla Knorr, Hans Morch Jensen, Lars Vedel Kessing
    Abstract:

    AbstractBackground: Rating scales used to assess the severity of depression e.g. the Hamilton Depression Rating Scale 17-item (HDRS-17) partly rely on the patient's subjective experience and reporting. Such subjective measures tend to have low reliability and adding objective measures to complement the assessment of depression severity would be a major step forward. Aims: To investigate correlations between electronic monitoring of Psychomotor Activity and severity of depression according to HDRS-17. Methods: A total of 36 patients with unipolar disorder (n = 18) or bipolar disorder (n = 18) and 31 healthy control persons aged 18–60 years were included. Psychomotor Activity was measured using a combined heart rate and movement sensor device (Actiheart) for 3 consecutive days, 24 h a day. Results: We found that sleeping heart rate (beats/min) correlated with HDRS-17 in both patients with unipolar disorder and bipolar disorder (unadjusted model: B = 0.46, 95% CI 0.037–0.89, P = 0.034). In contrast, correlat...

  • differences in Psychomotor Activity in patients suffering from unipolar and bipolar affective disorder in the remitted or mild moderate depressive state
    Journal of Affective Disorders, 2012
    Co-Authors: Maria Faurholtjepsen, Soren Brage, Maj Vinberg, Ellen Margrethe Christensen, Ulla Knorr, Hans Morch Jensen, Lars Vedel Kessing
    Abstract:

    Abstract Background Abnormalities in Psychomotor Activity are a central and essential feature of affective disorder. Studies measuring differences in Psychomotor Activity between unipolar and bipolar disorder show divergent results and none have used a combined heart rate and movement monitor for measuring Activity during free-living conditions. Objective To compare objectively measured Psychomotor Activity in patients with unipolar and bipolar disorder in a remitted or mild/moderate depressive state. Further, both groups were compared to a healthy control group. Methods A cross-sectional study of outpatients suffering from unipolar (n = 20) and bipolar (n = 18) disorder and healthy controls (n = 31), aged 18–60 years. For three consecutive days a combined acceleration (m/s2) and heart rate (beats per minute) monitoring was used in conjunction with a step test to estimate Activity energy expenditure (J/min/kg) as measures of Psychomotor Activity and physical fitness. Results Overall score on Hamilton-17 items ranged between 0 and 22. Patients had higher sleeping heart rate (p  Conclusions Electronic monitoring of Psychomotor Activity may be a promising additional tool in the distinction between unipolar and bipolar affective disorder when patients present in a remitted or depressive state.

M. Angelica De Souza Silva - One of the best experts on this subject based on the ideXlab platform.

  • Neurokinin(3) receptor modulation of the behavioral and neurochemical effects of cocaine in rats and monkeys
    Reviews in the Neurosciences, 2008
    Co-Authors: M. Angelica De Souza Silva, Gerhard Jocham, Marilia Barros, Carlos Tomaz, Christian P. Müller
    Abstract:

    Neurokinin3 (NK3) receptors and their endogenous ligands (e.g. the neuropeptide substance P and its C-terminal fragment) have been implicated in Psychomotor Activity and reinforcement mechanisms. We review here recent findings on the involvement of NK3 receptors in the behavioral and neurochemical effects of cocaine. Although NK3 receptors can modulate dopamine (DA) Activity in the brain, recent results suggest that this modulation does not occur during spontaneous behavioral Activity. However, NK3 receptors play a role in the regulation of cocaine-induced DA responses in the nucleus accumbens core and shell subregions. NK3 receptor agonism as well as antagonism potentiate cocaine's effects on nucleus accumbens DA subregions specifically, and modulate the acute behavioral effects of cocaine in rats and non-human primates (Callithrix penicillata). However, conditioned place preference studies in rats have, so far, failed to provide evidence for an involvement of NK3 receptors in the reinforcing effects of cocaine.

  • Neurokinin 3 receptor activation potentiates the Psychomotor and nucleus accumbens dopamine response to cocaine, but not its place conditioning effects.
    European Journal of Neuroscience, 2007
    Co-Authors: Gerhard Jocham, Joseph P. Huston, Christian P. Müller, Andrea C. Lauber, M. Angelica De Souza Silva
    Abstract:

    Neurokinin 3 receptors (NK 3 -Rs) have been implicated in Psychomotor Activity and reinforcement mechanisms. Recently, we showed that NK 3 -R antagonism blocked the psychostimulant properties of cocaine both in rats and in primates. Here, using in vivo microdialysis in the nucleus accumbens (NAc) of freely moving rats, we investigated the effect of the NK 3 -R agonist senktide (0.2 and 0.4 mg/kg s.c.) on the cocaine-evoked increase in dopamine. Cocaine (10 mg/kg i.p.) increased dopamine levels to 404 and 480% of baseline in the core and shell of the NAc, respectively. Pretreatment with senktide at a dose of 0.2 mg/kg potentiated this effect to 666 (core) and 869% (shell) of baseline, without having any effect on dopamine when given alone. Behavioural measurements revealed that 0.2 mg/kg senktide also potentiated the cocaine-induced increase in horizontal and vertical Activity. Senktide alone induced a short-lasting increase in Activity that was not accompanied by any alterations of the neurochemical parameters. In conditioned place preference (CPP) experiments, senktide pretreatment did not alter CPP induced by cocaine (5 and 10 mg/kg i.p.), and had no effect when given alone. Likewise, cocaine-conditioned locomotor Activity was not affected by the NK 3 -R agonist. However, as in the microdialysis studies, cocaine-induced (5 and 10 mg/kg i.p.) hyperActivity was potentiated by senktide, and there was evidence for a facilitation of sensitization to the hyperlocomotor effects of cocaine by senktide. These data provide evidence that NK 3 -Rs are involved in the control of the hyperlocomotor and NAc DA response to cocaine, but not in cocaine-induced CPP.