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Conan Kornetsky - One of the best experts on this subject based on the ideXlab platform.
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Effects of morphine on Brain-Stimulation Reward thresholds in young and aged rats
Pharmacology biochemistry and behavior, 2004Co-Authors: Shivkumar H. Jha, Clifford M. Knapp, Conan KornetskyAbstract:Mesolimbic opioid systems are altered with aging; however, the effects of these changes on the Rewarding actions of opioids have not been examined. The present experiment assessed differences in the responsiveness of Brain Reward pathways in young and aged rats to the effects of morphine using the Brain-Stimulation Reward (BSR) model. Aged (24 months) and young (5 months) male F344/BNF1 rats were stereotaxically implanted with a bipolar stainless steel electrode into the lateral hypothalamic (LH) region of the medial foreBrain bundle. Thresholds were determined using the rate-independent psychophysical method. Each animal was tested after the administration of saline or morphine at 0.5, 1, 2.5, 5 and 10 mg/kg doses. A significant difference in the mean baseline threshold between aged (99.8+/-6 microA) and young rats (149.1+/-14 microA) was observed. Although in both groups morphine lowered the BSR threshold, there were no significant differences between the groups except at the 10-mg/kg dose, the difference did approach significance. This study indicates that there are baseline differences in the Rewarding threshold in the two groups, that morphine lowers the threshold in young and aged animals and that the hedonic effects produced by morphine, for the most, part remain preserved in aged animals.
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The effects of cocaine on the rate independent Brain Stimulation Reward threshold in the mouse.
Pharmacology biochemistry and behavior, 2004Co-Authors: Brian M. Gill, Clifford M. Knapp, Conan KornetskyAbstract:Interest in the development of mouse models of drug abuse liability has increased with the introduction of selective gene expression. In the rat, the ability of drugs to lower Brain Stimulation Reward (BSR) thresholds often correlates with high abuse liability. Measurement of BSR thresholds using rate-independent methods decreases the influence of impaired motor performance on threshold determination that may confound studies of mutant mice. In the present experiment, the effects of cocaine on mouse BSR thresholds were assessed using a modification of the rate-independent psychophysical method of limits as current intensity was systematically varied in a series of descending and ascending discrete trials. Bipolar electrodes were implanted into the medial foreBrain bundle of male C57Bl/6N mice and the effects of intraperitoneal saline and cocaine (5.0-30.0 mg/kg) on BSR thresholds were assessed using a within-subject crossover design. Threshold was defined as the intensity at which the mouse would respond in 50% of the trials. Threshold levels were significantly lowered below levels of control following cocaine administration with the maximum lowering following a 20.0-mg/kg dose. These findings indicate that cocaine increases the sensitivity of the mouse to BSR, and that BSR thresholds can be determined using rate-independent methods in this species.
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Gamma-vinyl GABA attenuates cocaine-induced lowering of Brain Stimulation Reward thresholds.
Psychopharmacology, 1997Co-Authors: Stephanie A. Kushner, Stephen L. Dewey, Conan KornetskyAbstract:Gamma-vinyl GABA (GVG, also referred to as vigabatrin), an irreversible inhibitor of GABA transaminase (GABA-T), raises levels of GABA in nerve terminals, inhibits striatal dopamine release, and attenuates cocaine-induced increases in extracellular dopamine in the striatum and nucleus accumbens. In order to determine the action of GVG on dopamine-mediated Reward, we examined its effects on the threshold for Rewarding Brain Stimulation in male F-344 rats. GVG dose-dependently raised Brain Stimulation Reward (BSR) thresholds at doses of 200, 300, and 400 mg/kg without significant effects on motor performance as measured by response latencies. In order to determine if GVG had similar modulatory effects on cocaine-induced lowering of BSR thresholds, the effective doses of GVG were co-administered with 2.5 and 5.0 mg/kg cocaine, doses that significantly lower BSR thresholds. The 400 mg/kg dose of GVG significantly blocked the lowering of thresholds seen at each dose of cocaine. Cocaine in combination with 200 or 300 mg/kg GVG, doses of GVG that significantly raise BSR thresholds, resulted in thresholds not significantly different from those obtained with cocaine alone. These data demonstrate that, at the doses tested, GVG is more effective at modulating basal Reward thresholds than at modulating thresholds lowered by cocaine, implying that as dopaminergic activity increases, GABAergic activity must also increase in order to exert its inhibitory influence on dopaminergic activity.
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DAMGO and DPDPE facilitation of Brain Stimulation Reward thresholds is blocked by the dopamine antagonist cis-flupenthixol
Neuropharmacology, 1997Co-Authors: Christine L. Duvauchelle, Sheila M. Fleming, Conan KornetskyAbstract:Summary The role of dopamine neurotransmission in opioid Reward was investigated using a rateindependent measure for determining Brain Stimulation Reward (BSR) thresholds. Intra-accumbens infusions of the μ- and δ-specific peptides, D-Ala2, N-Me-Phe4, Gly-ol5-Enkephalin and D-Pen2, d -Pen5-Enkephalin caused significant lowering of BSR thresholds. The dopamine D1/D2 antagonist, cis-flupenthixol, blocked these effects at a dose that did not significantly alter thresholds when given alone. These data suggest both μ- and δ-opioid potentiation of BSR is dopamine dependent.
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Involvement of δ- and μ-opioid receptors in the potentiation of Brain-Stimulation Reward
European journal of pharmacology, 1996Co-Authors: Christine L. Duvauchelle, Sheila M. Fleming, Conan KornetskyAbstract:Abstract A rate-free method of determining Brain-Stimulation Reward thresholds was used to identify the Rewarding effects of the δ-opioid receptor and μ-opioid receptor agonist peptides, [ d -Pen 2 , d -Pen 5 ]enkephalin (DPDPE) and [ d -Ala 2 -MePhe 4 -Gly(ol) 5 ]enkephalin (DAMGO). The nucleus accumbens-delivered opioid receptor agonists produced marked lowering of the threshold for ventral tegmental area Brain-Stimulation Reward. No change in baseline thresholds was seen after peripheral administration of the nonpeptide δ-opioid receptor antagonist, naltrindole. However, an unexpected finding was that naltrindole blocked the threshold-lowering effects of both DPDPE and DAMGO. These data demonstrate nucleus accumbens activation of δ- and μ-opioid receptors and ventral tegmental area Brain-Stimulation Reward share common Brain substrates. In addition, the interference of both δ- and μ-opioid receptor mediated Reward by naltrindole may have implications for therapeutic use.
Pierre-paul Rompré - One of the best experts on this subject based on the ideXlab platform.
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Cannabinoids Reward sensitivity in a neurodevelopmental animal model of schizophrenia: A Brain Stimulation Reward study
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2014Co-Authors: Alexandra Gallo, Claude Bouchard, Emmanuel Fortier, Charles Ducrot, Pierre-paul RompréAbstract:The comorbidity schizophrenia and cannabis has a high prevalence. The consumption of cannabis is ten times higher among schizophrenia patients, suggesting that these patients could be differentially sensitive to its motivational effects. To study this question, we investigated the motivational effects of cannabinoid agonists using the Brain Stimulation Reward paradigm and a neurodevelopmental model of schizophrenia: neonatal ventral hippocampus lesions (NVHL). Using the curve-shift paradigm, we first compared the effect single dose (0.75mg/kg) of amphetamine in sham and NVHL rats on Reward and operant responding. Then, in different groups of NVHL and sham rats, we studied the effect of delta-9-tetrahydrocannabinnol (THC, 0.5mg/kg, i.p.) and WIN55,212-2 (WIN, 1 and 3mg/kg, i.p.) Rats were initially trained to self-administer an electrical Stimulation to the posterio-medial mesencephalon. Once responding was stable, Reward threshold defined as the frequency required to induce a half maximum response rate was measured before and after injection of the drug or the vehicle. Results show that amphetamine enhanced Reward in sham and NVHL rats, an effect that was shorter in duration in NVHL rats. THC produced a weak attenuation of Reward in sham rats while WIN produced a dose-dependent attenuation in NVHL; the attenuation effect of WIN was blocked by the cannabinoid antagonist, AM251. WIN also produced an attenuation of performance in sham and NVHL rats, and this effect was partially prevented by AM251. These results provide the additional evidence that the motivational effect of cannabinoids is altered in animals with a schizophrenia-like phenotype.
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Blockade of mGLUR5 receptors differentially alters amphetamine-induced enhancement of locomotor activity and of Brain Stimulation Reward.
Journal of psychopharmacology (Oxford England), 2010Co-Authors: Stéphanie Gormley, Pierre-paul RompréAbstract:This study was aimed at determining the role of mGLUR5 glutamate receptors on amphetamine-induced enhancement of locomotion and of Brain Stimulation Reward (BSR). The effect of different doses of the mGLUR5 antagonist, MPEP (0, 1, 3 and 9 mg/kg, i.p.), was assessed on Reward induced by electrical Stimulation of the lateral hypothalamus, and on the enhancement of Reward by amphetamine (1 mg/kg, i.p.) in adult male Long Evans rats. The effect of a single dose of MPEP (0 and 9 mg/kg) on amphetamine-induced increase in locomotor activity was also assessed. Systemic injection of MPEP alone did not alter Reward threshold and maximum rate of responding. Amphetamine produced a 25-30% decrease in Reward threshold, an effect not altered by the highest dose of MPEP. At this dose, MPEP produced a weak inhibition of spontaneous locomotion and a significant attenuation of the enhanced locomotor activity induced by amphetamine. These findings show that mGLUR5 glutamate receptors are unlikely to constitute important elements of the Reward-relevant pathway, and do not intervene in the enhancement effect of amphetamine. They also show, however, that these glutamate receptors play a key role in amphetamine-induced increased locomotor activity, providing additional evidence for a dissociation between the substrates that mediate these two behaviours.
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Quetiapine blocks cocaine-induced enhancement of Brain Stimulation Reward.
Behavioural brain research, 2009Co-Authors: Alexandra Gallo, Stéphanie Lapointe, Emmanuel Stip, Stéphane Potvin, Pierre-paul RompréAbstract:Quetiapine is an effective atypical antipsychotic medication that was reported to reduce substance use and craving in patients with schizophrenia. This clinical effect of quetiapine is hypothesized to be due to its low affinity for dopamine receptors and its weak attenuation of central Reward functions. The present study was designed to determine the magnitude of the Reward attenuation induced by different doses of quetiapine and its effectiveness at reducing the effect of cocaine. Experiments were performed on male Sprague-Dawley rats that were trained to produce operant responses to receive Rewarding Stimulations to the medial foreBrain bundle. In a first study, we tested the effects of three doses of quetiapine (5, 10, 20 mg/kg) on Brain Stimulation Reward using a within-subject design and the curve-shift method. In a second study, we tested the effectiveness of a low and high dose of quetiapine (5 and 20 mg/kg) at blocking the Reward enhancing effect of cocaine (4 mg/kg) in different groups of animals. Quetiapine produced a weak (20%) but significant attenuation of Reward. Cocaine enhanced Reward by 20% and the combination of cocaine with the high dose of quetiapine lead to cancellation of each drug effect. The low dose of quetiapine did not alter baseline Reward but completely blocked the effect of cocaine. The magnitude of the Reward attenuation induced by quetiapine is consistent with its low affinity for dopamine receptors. Its actions on dopamine and non-dopamine neurotransmission are likely to account for its effectiveness at blocking the enhancement of Reward by cocaine.
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Effects of the dopamine stabilizer, OSU-6162, on Brain Stimulation Reward and on quinpirole-induced changes in Reward and locomotion.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2009Co-Authors: Faïza Benaliouad, Shitij Kapur, Sridhar Natesan, Pierre-paul RompréAbstract:Dysregulation of limbic dopamine (DA) neurotransmission results in abnormal positive or negative emotional states that characterize several mental disorders. Drugs that restore DA homeostasis are most likely to constitute effective treatments for such emotional disturbances. In this study, we investigated the effects of several doses of OSU-6162, a drug that belongs to a new class named “DA stabilizers”, on Brain Stimulation Reward. Because quinpirole produces, depending on the dose, a pre-synaptic depressant and a post-synaptic stimulatory effect on Reward and locomotor activity, we also compared the ability of OSU-6162 and haloperidol to prevent these effects of the full DA agonist. Results show that OSU-6162 produced a dose-orderly reduction of Reward with no change in the capacity of the animals to produce the operant response, and prevented, like haloperidol, both stimulatory and depressant effects of quinpirole on locomotor activity but only its Reward stimulatory effect. The observed functional antagonism of OSU-6162 on these DA-dependent behaviors suggests that it may constitute an effective treatment for abnormal positive emotional state, and that it would be exempt of motor side-effects.
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Effects of neurotensin receptor activation on Brain Stimulation Reward in Fischer 344 and Lewis rats
European journal of pharmacology, 2001Co-Authors: Pat Bauco, Pierre-paul RompréAbstract:The effects of intracerebroventricular injections of 18 nmol/10 microl of neurotensin, [D-Tyr(11)]neurotensin, or saline on operant responding for Brain Stimulation Reward were investigated in Fischer 344 (F344) and Lewis (LEW) rats using the curve-shift paradigm. [D-Tyr(11)]neurotensin, but not neurotensin, decreased Reward threshold in F344 rats while it increased thresholds in LEW rats. Both peptides suppressed maximal rates of responding; this effect was of greater magnitude and longer lasting in LEW than in F344 rats. These findings show that F344 and LEW rat strains are differentially sensitive to activation of central neurotensin receptors that modulate Reward-relevant circuitry.
Catherine Bielajew - One of the best experts on this subject based on the ideXlab platform.
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Investigating the hedonic effects of interferon-α on female rats using Brain-Stimulation Reward
Behavioural brain research, 2006Co-Authors: Amanda C. Kentner, Jonathan S. James, Maı̈a Miguelez, Catherine BielajewAbstract:Interferon-alpha (IFN-alpha) is used as a front-line treatment for cancer and other diseases. Reports of depression as a consequence of IFN-alpha therapy scatter the literature, generating interest in the CNS disruptions elicited by this cytokine. In the present work, we investigated the short- and long-term effects of a single systemic injection of vehicle, 10, or 1000 units of IFN-alpha on temperature, body weight, food intake, sickness behaviours, locomotor activity, and Brain Stimulation Reward (BSR) thresholds elicited from the ventral tegmental area in female Long-Evans rats. Pioneered for studying motivational processes, BSR has been exploited as a tool for tracking hedonic status in animal models of depression. In this study, the main findings were that IFN-alpha did not induce anhedonia as defined by no increase in frequency thresholds. However, the analyses of sickness behaviours unveiled a significant increase in piloerection in all sham control animals that received an IFN-alpha injection while the BSR animal scores remained relatively unchanged between pre- and post-injection days. This pattern was also evident in the overall total sickness behaviour scores. Our data suggest that a single exposure to IFN-alpha treatment in female rats elicits long-term somatic effects, without altering hedonic status.
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Mapping the neural substrate underlying Brain Stimulation Reward with the behavioral adaptation of double-pulse methods.
Reviews in the neurosciences, 2004Co-Authors: Maı̈a Miguelez, Catherine BielajewAbstract:Behavioral adaptations of double-pulse methods--primarily collision and refractory period tests--have been employed to unveil the electrophysiological and anatomical characteristics of neural networks of known function. These paradigms are based on trade-off functions: a determination of different combinations of stimuli that yield the same behavioral output. A detailed explanation of the logic and methodology underlying these techniques is elaborated in this paper. The implementation of such approaches to the study of Brain Stimulation Reward (BSR) has provided a means of discriminating between the neurons underlying this behavior from other cells activated by the stimulating electrode, endowing them with a particularly powerful scientific scope. An increasingly detailed portrait of the BSR substrate, both within and outside the medial foreBrain bundle, has been emerging as a result of these investigations and is reviewed in this paper. Finally, the challenges associated with these paradigms are discussed and potential solutions as well as future experimental ventures proposed. Attention is drawn to the major contribution of these methods to our understanding of the neural pathways and characteristics underlying BSR.
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Measuring threshold shifts for Brain Stimulation Reward using the method of limits.
Canadian journal of experimental psychology = Revue canadienne de psychologie experimentale, 2001Co-Authors: Anne T. M. Konkle, Catherine Bielajew, George Fouriezos, Annette ThrasherAbstract:Abstract Thresholds determined from the frequency of pulses and the current for Rewarding Brain Stimulation were obtained from rats with lateral hypothalamic electrodes. The threshold, defined as the frequency or current corresponding to one-half the maximum response rate, was interpolated from Reward summation functions. Daily trials of both ascending and descending sequences of frequency and current yielded no significant difference between order of presentation. While there was more variability in the maximum response rates across the sessions, neither frequency- nor current-based threshold evaluations yielded significant rate effects. Our findings suggest that the threshold procedure is generally not influenced by the sequence of delivery of stimulus values and, thus, may be regarded as a reliable measure of the reinforcing properties of Brain-Stimulation Reward. Less than a decade after Olds and Milner (1954) reported that electrical Stimulation applied to certain Brain structures had Rewarding properties, researchers began investigating methods other than that of measuring simply response rates for assessing and quantifying the Rewarding effect (Valenstein, 1964). Early on, it was recognized that a variety of factors unrelated to Reward influence the rate at which an animal will respond for Brain Stimulation. This makes a single measure of Reward inadequate. While other means of evaluating Reward value have been explored, it is the adaptation of classical psychophysical methods for detecting the threshold associated with a constant level of responding that has endured (Liebman, 1983). The most direct of these is the "method of limits" (Kling & Riggs, 1971). Investigators interested in tracing and characterizing the neural circuitry underlying Brain Stimulation Reward further refined these methods by employing trade-off functions that show the relationship between two parameters - for example, the Stimulation current and the Stimulation frequency (elaborated in Gallistel, Shizgal, & Yeomans, 1981). The psychophysically derived trade-off function is believed to mirror the activity of the first-stage, or directly stimulated, Reward neurons. The logic underlying this belief is the same as that for the trade-off between light intensity and frequency in dark-adapted participants that is understood to reflect the trade-off (absorption spectrum) of intensity and frequency of the isolated photopigment, rhodopsin, a much-cited example from vision psychophysics (see Stellar & Stellar, 1985). This direction towards a more quantitative approach was pivotal to the development of paradigms aimed at inferring the neurophysiological characteristics of neurons, including conduction velocity (Bielajew, Bushnik, Konkle, & Schindler, 2000; Bielajew, Jordan, Ferme-Enright, & Shizgal, 1981; Bielajew, Konkle, Fouriezos, & Boucher-Thrasher, 2001; Bielajew & Shizgal, 1980, 1982, 1986; Boye & Rompre, 1996; Shizgal, Bielajew, Corbett, Skelton, & Yeomans, 1980; Trzifiska & Bielajew, 1998), refractory period (Bielajew, Bushnik, Konkle, & Parkin, 1999; Bielajew et al., 1981; Bielajew, Konkle, Fouriezos, BoucherThrasher, & Schindler, 2001; Bielajew, Lapointe, Kiss, & Shizgal, 1982; Bielajew & Shizgal, 1982; Fouriezos, Walker, Rick, & Bielajew, 1987; Trzifiska and Bielajew, 1992; Yeomans, 1975, 1979; Yeomans, Matthews, Hawkins, Bellman, & Doppelt, 1979), and current-distance relations (Fouriezos & Wise, 1984). From these studies, a portrait has emerged suggesting that the substrate for Brain Stimulation Reward comprises small myelinated neurons, some of which project from the lateral preoptic area directly to the lateral hypothalamus and which, via synaptic connections, descend to the ventral tegmental area. The basic measurement tool from which the above data derive is threshold evaluation. The variable that is typically scaled in this procedure is the frequency of pulses per train in order to determine the value that corresponds to a constant level of performance. …
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The substrate for Brain-Stimulation Reward in the lateral preoptic area. I. Anatomical mapping of its boundaries.
Brain research, 2000Co-Authors: Tamara Bushnik, Catherine Bielajew, Anne T. M. KonkleAbstract:Given the putative role of the lateral preoptic area as a primary contributor of the cell bodies of origin of the descending pathway linking a subset of lateral hypothalamic and ventral tegmental area Reward neurons, the distribution of self-Stimulation sites in this structure was mapped in 22 animals using moveable electrodes and threshold procedures. Ninety-seven electrode sites were evaluated with placements ranging from just rostral to the midline convergence of the anterior commissure back to the transition zone between the lateral preoptic and lateral hypothalamic areas; of these, roughly 2/3 supported self-Stimulation which was widely observed throughout the lateral preoptic area and medial foreBrain bundle. In general, self-Stimulation thresholds obtained from lateral sites were most stable, and progressively so approaching more caudal regions. Examination of the slopes of the period/current trade-off functions revealed a tendency for higher values in lateral and caudal sites; in contrast, dorsoventral excursions did not influence these estimates. Taken together, these data provide support for the notion that the substrate for Brain-Stimulation Reward in the lateral preoptic area has a relatively homogeneous distribution that is more diffusely organized than that found in Reward sites activated further caudally in the medial foreBrain bundle.
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The substrate for Brain-Stimulation Reward in the lateral preoptic area. II. Connections to the ventral tegmental area.
Brain research, 2000Co-Authors: Catherine Bielajew, Anne T. M. Konkle, Tamara Bushnik, Dwayne SchindlerAbstract:This experiment investigated the existence of a direct anatomical connection between lateral preoptic and ventral tegmental areas that mediate Brain Stimulation Reward using the behavioral adaptation of the collision test. This test is a double-pulse, two-electrode technique based on the axonal conduction failure that occurs when two separate sites in the same axon bundle are concurrently stimulated. This anatomical arrangement is inferred from the shape of the function relating the effectiveness of double-pulse Stimulation to the interval between pulses. In this study, nine rats with a total of 44 pairs of sites were examined. In two pairs only was there a profile suggestive of an axonal collision effect, while the double-pulse effectiveness curve consistent with the properties of transynaptic collision was apparent for a single pair of sites; the remaining 93% were associated with relatively flat effectiveness curves. While electrode misalignment could be responsible for these results, there was adequate sampling to suggest that the preponderance of first stage signals that give rise to the Rewarding effects mediated by the lateral preoptic and ventral tegmental areas do not travel along the same fiber bundle. However, Stimulation applied to both sites concurrently produces a summation that is roughly 40% greater than Stimulation at either site alone, suggesting reasonable integration of the Reward signals generated by lateral preoptic and ventral tegmental area Stimulation.
Hweihsien Chen - One of the best experts on this subject based on the ideXlab platform.
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Attenuation of toluene-induced Brain Stimulation Reward enhancement and behavioral disturbances by N-acetylcysteine in mice.
Toxicology, 2018Co-Authors: Yi-lin Tsai, Minghuan Chan, Chung-pin Hsieh, Tsui Chin Wang, Hweihsien ChenAbstract:Toluene, a commonly used organic solvent, produces a variety of behavioral disturbances in both humans and animals comparable to noncompetitive N-methyl-D-aspartate receptor (NMDARs) antagonists, such as phencyclidine (PCP). N-acetylcysteine (NAC) is capable of reversing the psychotomimetic effects of PCP via activation of cystine-glutamate antiporters (xCT). The present study examined whether NAC is capable of attenuating the toluene-induced Brain Stimulation Reward enhancement and behavioral manifestations. Male mice received various doses of NAC prior to toluene exposure for assessment of intracranial self-Stimulation (ICSS) thresholds, rotarod test, novel object recognition task and social interaction test. NAC ameliorated the lowering of ICSS thresholds, motor incoordination, object recognition memory impairments and social withdrawal induced by toluene. Furthermore, the capacity of NAC to ameliorate acute toluene-induced deficits in object recognition and social interaction was blocked by the xCT inhibitor (S)-4-carboxyphenylglycine and the mGluR2/3 antagonist LY341495. These results indicate that NAC could prevent toluene-induced Reward facilitation and behavioral disturbances and its beneficial effects, at least for cognitive function and social interaction, are associated with activation of the xCT and mGluR2/3. These findings show the potential promise for NAC to treat toluene dependence and to prevent toluene intoxication caused by unintentional or deliberate inhalation.
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sarcosine attenuates toluene induced motor incoordination memory impairment and hypothermia but not Brain Stimulation Reward enhancement in mice
Toxicology and Applied Pharmacology, 2012Co-Authors: Minghuan Chan, Shiangsheng Chung, Astrid K Stoker, Hweihsien Chen, Athina MarkouAbstract:Abstract Toluene, a widely used and commonly abused organic solvent, produces various behavioral disturbances, including motor incoordination and cognitive impairment. Toluene alters the function of a large number of receptors and ion channels. Blockade of N -methyl- d -aspartate (NMDA) receptors has been suggested to play a critical role in toluene-induced behavioral manifestations. The present study determined the effects of various toluene doses on motor coordination, recognition memory, body temperature, and intracranial self-Stimulation (ICSS) thresholds in mice. Additionally, the effects of sarcosine on the behavioral and physiological effects induced by toluene were evaluated. Sarcosine may reverse toluene-induced behavioral manifestations by acting as an NMDA receptor co-agonist and by inhibiting the effects of the type I glycine transporter (GlyT1). Mice were treated with toluene alone or combined with sarcosine pretreatment and assessed for rotarod performance, object recognition memory, rectal temperature, and ICSS thresholds. Toluene dose-dependently induced motor incoordination, recognition memory impairment, and hypothermia and lowered ICSS thresholds. Sarcosine pretreatment reversed toluene-induced changes in rotarod performance, novel object recognition, and rectal temperature but not ICSS thresholds. These findings suggest that the sarcosine-induced potentiation of NMDA receptors may reverse motor incoordination, memory impairment, and hypothermia but not the enhancement of Brain Stimulation Reward function associated with toluene exposure. Sarcosine may be a promising compound to prevent acute toluene intoxications by occupational or intentional exposure.
Sandra M. Boye - One of the best experts on this subject based on the ideXlab platform.
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Electrolytic lesions of the habenula attenuate Brain Stimulation Reward.
Behavioural brain research, 2007Co-Authors: Marie-claude Morissette, Sandra M. BoyeAbstract:The present experiment used electrolytic lesions in combination with curve-shift scaling to study the functional relation between the habenula and four different Brain sites that support operant responding for Brain Stimulation Reward. Rats were implanted with a monopolar Stimulation electrode aimed at the lateral hypothalamus, ventral tegmental area, dorsal raphe or median raphe nuclei, and a lesioning electrode in the ipsilateral habenula. Operant nose poking resulted in self-administration of trains of electrical pulses to one of the above Stimulation sites. Reward thresholds were derived from response-number curves and defined as the pulse number necessary for half-maximal responding. Rats were tested daily at each of three current intensities that were chosen from individual number-current trade-off functions and that yielded baseline Reward thresholds of approximately 10, 20 and 40 pulses/train. Testing resumed 24h after lesioning the habenula (100 muA anodal current, 20-25s) and continued for 3-4 weeks. A total of 19 rats completed the experiment. In five of these, habenular lesions clearly reduced the Rewarding effectiveness of the Stimulation; Reward thresholds increased by approximately 30-245% (0.12-0.54 log10 units). Generally, lesion effects were observed at low and medium current intensities, developed gradually and did not recover. Histological analysis revealed that in two rats the Stimulation electrode was located in the posterior lateral hypothalamus, two in the anterior ventral tegmental area and one in the area of the dorsal raphe. These results strongly suggest that the habenula constitutes an important component of the neural circuitry important for Brain Stimulation Reward.
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Opposite effects of mesencephalic microinjections of cholecystokinin octapeptide and neurotensin-(1-13) on Brain Stimulation Reward.
European journal of pharmacology, 1993Co-Authors: Pierre-paul Rompré, Sandra M. BoyeAbstract:Changes in operant responding for Brain Stimulation Reward were studied before and after a microinjection of 1 nmol of sulphated cholecystokinin octapeptide, neurotensin or saline into the ventral tegmental area. Neurotensin produced a significant and long lasting decrease in the Stimulation frequency required to produce a half-maximal rate of responding; cholecystokinin had the opposite effect, attenuating the Rewarding efficacy the Stimulation during the first 30 min post-injection. It is suggested that the opposite effects of the peptides on Reward are due to their differential modulatory effects on a subpopulation of mesencephalic dopamine neurones.