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  1. Article ; Online: Repeated phencyclidine disrupts nicotinic acetylcholine regulation of dopamine release in nucleus accumbens: Implications for models of schizophrenia.

    Yavas, Ersin / Young, Andrew M J

    Neurochemistry international

    2020  Volume 140, Page(s) 104836

    Abstract: Dopaminergic dysregulation in nucleus accumbens has been implicated in the origin of schizophrenia. Accumbal cholinergic interneurons exert powerful modulatory control of local dopamine function, through nicotinic receptors located on dopamine terminals. ...

    Abstract Dopaminergic dysregulation in nucleus accumbens has been implicated in the origin of schizophrenia. Accumbal cholinergic interneurons exert powerful modulatory control of local dopamine function, through nicotinic receptors located on dopamine terminals. Fast-scan cyclic voltammetry in rat brain slices in vitro was used to measure dopamine release evoked by high-frequency electrical stimulation, mimicking phasic dopamine activity. We investigated whether cholinergic regulation of stimulated dopamine release was disrupted by pretreatment with phencyclidine, a non-competitive NMDA receptor antagonist, which provides a well validated animal model of schizophrenia. Dihydro-β-erythroidine, an antagonist at β2-subuit containing nicotinic receptors, caused a concentration-dependent enhancement of stimulated dopamine release, indicating cholinergic inhibitory control over dopamine release. The agonist, nicotine, also caused concentration-dependent increases in release, consistent with rapid desensitisation of the receptors previously described. In slices taken from animals pretreated with phencyclidine, the augmentation of electrically-stimulated dopamine release elicited by both drugs was attenuated, particularly when each drug was applied at high concentration. In addition, the concentration-dependence of each drug effect was lost. Taken together these findings indicate that pretreatment with phencyclidine causes changes in acetylcholine systems modulating dopamine release in accumbens. Since phencyclidine treatment was terminated at least a week before the slices were taken, the effects are due to long-term changes in function resulting from the treatment, rather than from transient changes due to the presence of the drug at test. Such enduring dysregulation of cholinergic control of phasic dopamine release could account for deficits in behaviours mediated by accumbal dopamine seen in schizophrenia, and may provide a route for novel therapeutic strategies to treat the disease.
    MeSH term(s) Animals ; Dihydro-beta-Erythroidine/pharmacology ; Dopamine/metabolism ; Dose-Response Relationship, Drug ; Excitatory Amino Acid Antagonists/administration & dosage ; Excitatory Amino Acid Antagonists/toxicity ; Female ; Nucleus Accumbens/drug effects ; Nucleus Accumbens/metabolism ; Phencyclidine/administration & dosage ; Phencyclidine/toxicity ; Rats ; Rats, Wistar ; Receptors, Nicotinic/metabolism ; Schizophrenia/chemically induced ; Schizophrenia/metabolism
    Chemical Substances Excitatory Amino Acid Antagonists ; Receptors, Nicotinic ; nicotinic receptor beta2 ; Dihydro-beta-Erythroidine (23255-54-1) ; Phencyclidine (J1DOI7UV76) ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2020-08-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 283190-9
    ISSN 1872-9754 ; 0197-0186
    ISSN (online) 1872-9754
    ISSN 0197-0186
    DOI 10.1016/j.neuint.2020.104836
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    Zs.A 1610: Show issues Location:
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  2. Article ; Online: Attenuation of Stimulated Accumbal Dopamine Release by NMDA Is Mediated through Metabotropic Glutamate Receptors.

    Spencer, Felicity S E / Glodkowska, Maria / Sebold, Anna I / Yavas, Ersin / Young, Andrew M J

    ACS chemical neuroscience

    2023  

    Abstract: Electrically stimulated dopamine release from the nucleus accumbens is attenuated following application ... ...

    Abstract Electrically stimulated dopamine release from the nucleus accumbens is attenuated following application of
    Language English
    Publishing date 2023-04-06
    Publishing country United States
    Document type Journal Article
    ISSN 1948-7193
    ISSN (online) 1948-7193
    DOI 10.1021/acschemneuro.2c00777
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  3. Article ; Online: Metabotropic glutamate receptor modulation of dopamine release in the nucleus accumbens shell is unaffected by phencyclidine pretreatment: In vitro assessment using fast-scan cyclic voltammetry rat brain slices.

    Gupta, Ishan / Young, Andrew M J

    Brain research

    2018  Volume 1687, Page(s) 155–161

    Abstract: The non-competitive glutamate antagonist, phencyclidine is used in rodents to model behavioural deficits see in schizophrenia. Importantly, these deficits endure long after the cessation of short-term chronic treatment (sub-chronic), indicating that the ... ...

    Abstract The non-competitive glutamate antagonist, phencyclidine is used in rodents to model behavioural deficits see in schizophrenia. Importantly, these deficits endure long after the cessation of short-term chronic treatment (sub-chronic), indicating that the drug treatment causes long-term changes in the physiology and/or chemistry of the brain. There is evidence that this may occur through glutamatergic modulation of mesolimbic dopamine release, perhaps involving metabotropic glutamate receptors (mGluR). This study sought to investigate the effect of sub-chronic phencyclidine pretreatment on modulation of dopamine neurotransmission by metabotropic glutamate receptors 2 and 5 (mGluR2 and mGluR5) in the nucleus accumbens shell in vitro, with the hypothesis that phencyclidine pretreatment would disrupt the mGluR-mediated modulation of dopamine release. We showed that the orthosteric mGluR2 agonist LY379268 (0.1 µM, 1 µM and 10 µM) and mGluR5 positive allosteric modulator CDPPB (1 µM and 10 µM) both attenuated potassium-evoked dopamine release, underscoring their role in modulating dopamine neurotransmission in the nucleus accumbens. Sub-chronic PCP treatment, which caused cognitive deficits measured by performance in the novel object recognition task, modelling aspects of behavioral deficits seen in schizophrenia, induced neurobiological changes that enhanced dopamine release in the nucleus accumbens, but had no effect on mGluR2 or mGluR5 mediated changes in dopamine release. Therefore it is unlikely that schizophrenia-related behavioural changes seen after sub-chronic phencyclidine pre-treatment are mediated through mGluR modulation of dopamine release.
    MeSH term(s) Analysis of Variance ; Animals ; Animals, Newborn ; Dopamine/metabolism ; Electrochemical Techniques ; Excitatory Amino Acid Antagonists/pharmacology ; Female ; In Vitro Techniques ; Nucleus Accumbens/drug effects ; Phencyclidine/therapeutic use ; Potassium/pharmacology ; Rats ; Rats, Wistar ; Receptors, Metabotropic Glutamate/metabolism ; Recognition (Psychology)/drug effects
    Chemical Substances Excitatory Amino Acid Antagonists ; Receptors, Metabotropic Glutamate ; Phencyclidine (J1DOI7UV76) ; Potassium (RWP5GA015D) ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2018-03-07
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1200-2
    ISSN 1872-6240 ; 0006-8993
    ISSN (online) 1872-6240
    ISSN 0006-8993
    DOI 10.1016/j.brainres.2018.03.007
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    Zs.A 161: Show issues Location:
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  4. Article ; Online: Modulation of stimulated dopamine release in rat nucleus accumbens shell by GABA in vitro: Effect of sub-chronic phencyclidine pretreatment.

    Ferdinand, Jacqueline-Marie / Peters, Kate Z / Yavas, Ersin / Young, Andrew M J

    Journal of neuroscience research

    2021  Volume 99, Issue 7, Page(s) 1885–1901

    Abstract: Dopamine signaling in nucleus accumbens (NAc) is modulated by γ-aminobutyric acid (GABA), acting through GABA-A and GABA-B receptors: dysregulation of GABAergic control of dopamine function may be important in behavioral deficits in schizophrenia. We ... ...

    Abstract Dopamine signaling in nucleus accumbens (NAc) is modulated by γ-aminobutyric acid (GABA), acting through GABA-A and GABA-B receptors: dysregulation of GABAergic control of dopamine function may be important in behavioral deficits in schizophrenia. We investigated the effect of GABA-A (muscimol) and GABA-B (baclofen) receptor agonists on electrically stimulated dopamine release. Furthermore, we explored whether drug-induced changes were disrupted by pretreatment with phencyclidine, which provides a well-validated model of schizophrenia. Using brain slices from female rats, fast-scan cyclic voltammetry was used to measure electrically stimulated dopamine release in NAc shell. Both muscimol and baclofen caused concentration-dependent attenuation of evoked dopamine release: neither effect was changed by dihydro-β-erythroidine, a nicotinic acetylcholine receptor antagonist, or the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), precluding indirect mechanisms using these transmitter systems in the GABAergic actions. In slices taken from rats pretreated with phencyclidine, the attenuation of evoked dopamine release by baclofen was abolished, but the attenuation by muscimol was unaffected. Since phencyclidine pretreatment was followed by drug-free washout period of at least a week, the drug was not present during recording. Therefore, disruption of GABA-B modulation of dopamine is due to long-term functional changes resulting from the treatment, rather than transient changes due to the drug's presence at test. This enduring dysregulation of GABA-B modulation of accumbal dopamine release provides a plausible mechanism through which GABA dysfunction influences accumbal dopamine leading to behavioral changes seen in schizophrenia and may provide a route for novel therapeutic strategies to treat the condition.
    MeSH term(s) Animals ; Dopamine/metabolism ; Excitatory Amino Acid Antagonists/pharmacology ; Female ; GABA Agonists/pharmacology ; Nucleus Accumbens/drug effects ; Nucleus Accumbens/metabolism ; Phencyclidine/pharmacology ; Rats ; Rats, Wistar ; Schizophrenia/metabolism ; gamma-Aminobutyric Acid/metabolism
    Chemical Substances Excitatory Amino Acid Antagonists ; GABA Agonists ; gamma-Aminobutyric Acid (56-12-2) ; Phencyclidine (J1DOI7UV76) ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2021-04-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 195324-2
    ISSN 1097-4547 ; 0360-4012
    ISSN (online) 1097-4547
    ISSN 0360-4012
    DOI 10.1002/jnr.24843
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    Zs.A 1232: Show issues Location:
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  5. Article ; Online: Distracting stimuli evoke ventral tegmental area responses in rats during ongoing saccharin consumption.

    Peters, Kate Z / Young, Andrew M J / McCutcheon, James E

    The European journal of neuroscience

    2021  Volume 53, Issue 6, Page(s) 1809–1821

    Abstract: Disruptions in attention, salience and increased distractibility are implicated in multiple psychiatric conditions. The ventral tegmental area (VTA) is a potential site for converging information about external stimuli and internal states to be ... ...

    Abstract Disruptions in attention, salience and increased distractibility are implicated in multiple psychiatric conditions. The ventral tegmental area (VTA) is a potential site for converging information about external stimuli and internal states to be integrated and guide adaptive behaviours. Given the dual role of dopamine signals in both driving ongoing behaviours (e.g., feeding) and monitoring salient environmental stimuli, understanding the interaction between these functions is crucial. Here, we investigate VTA neuronal activity during distraction from ongoing feeding. We developed a task to assess distraction exploiting self-paced licking in rats. Rats trained to lick for saccharin were given a distraction test, in which three consecutive licks within 1 s triggered a random distractor (e.g. light and tone stimulus). On each trial they were quantified as distracted or not based on the length of their pauses in licking behaviour. We expressed GCaMP6s in VTA neurons and used fibre photometry to record calcium fluctuations during this task as a proxy for neuronal activity. Distractor stimuli caused rats to interrupt their consumption of saccharin, a behavioural effect which quickly habituated with repeat testing. VTA neural activity showed consistent increases to distractor presentations and, furthermore, these responses were greater on distracted trials compared to non-distracted trials. Interestingly, neural responses show a slower habituation than behaviour with consistent VTA responses seen to distractors even after they are no longer distracting. These data highlight the complex role of the VTA in maintaining ongoing appetitive and consummatory behaviours while also monitoring the environment for salient stimuli.
    MeSH term(s) Animals ; Behavior, Animal ; Dopamine ; Neurons ; Rats ; Saccharin ; Ventral Tegmental Area
    Chemical Substances Saccharin (FST467XS7D) ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2021-02-02
    Publishing country France
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 645180-9
    ISSN 1460-9568 ; 0953-816X
    ISSN (online) 1460-9568
    ISSN 0953-816X
    DOI 10.1111/ejn.15108
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    Zs.A 2548: Show issues Location:
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  6. Article ; Online: N-Methyl-d-aspartate Modulation of Nucleus Accumbens Dopamine Release by Metabotropic Glutamate Receptors: Fast Cyclic Voltammetry Studies in Rat Brain Slices in Vitro.

    Yavas, Ersin / Young, Andrew M J

    ACS chemical neuroscience

    2017  Volume 8, Issue 2, Page(s) 320–328

    Abstract: The N-methyl-d-aspartate (NMDA) receptor antagonist, phencyclidine, induces behavioral changes in rodents mimicking symptoms of schizophrenia, possibly mediated through dysregulation of glutamatergic control of mesolimbic dopamine release. We tested the ... ...

    Abstract The N-methyl-d-aspartate (NMDA) receptor antagonist, phencyclidine, induces behavioral changes in rodents mimicking symptoms of schizophrenia, possibly mediated through dysregulation of glutamatergic control of mesolimbic dopamine release. We tested the hypothesis that NMDA receptor activation modulates accumbens dopamine release, and that phencyclidine pretreatment altered this modulation. NMDA caused a receptor-specific, dose-dependent decrease in electrically stimulated dopamine release in nucleus accumbens brain slices. This decrease was unaffected by picrotoxin, making it unlikely to be mediated through GABAergic neurones, but was decreased by the metabotropic glutamate receptor antagonist, (RS)-α-methyl-4-sulfonophenylglycine, indicating that NMDA activates mechanisms controlled by these receptors to decrease stimulated dopamine release. The effect of NMDA was unchanged by in vivo pretreatment with phencyclidine (twice daily for 5 days), with a washout period of at least 7 days before experimentation, which supports the hypothesis that there is no enduring direct effect of PCP at NMDA receptors after this pretreatment procedure. We propose that NMDA depression of accumbal dopamine release is mediated by metabotropic glutamate receptors located pre- or perisynaptically, and suggest that NMDA evoked increased extrasynaptic spillover of glutamate is sufficient to activate these receptors that, in turn, inhibit dopamine release. Furthermore, we suggest that enduring functional changes brought about by subchronic phencyclidine pretreatment, modeling deficits in schizophrenia, are downstream effects consequent on chronic blockade of NMDA receptors, rather than direct effects on NMDA receptors themselves.
    MeSH term(s) Animals ; Animals, Newborn ; Dihydro-beta-Erythroidine/pharmacology ; Dopamine/metabolism ; Dose-Response Relationship, Drug ; Electric Stimulation ; Electrochemical Techniques ; Excitatory Amino Acid Agonists/pharmacology ; Excitatory Amino Acid Antagonists/pharmacology ; Female ; GABA Antagonists/pharmacology ; In Vitro Techniques ; N-Methylaspartate/pharmacology ; Nicotinic Antagonists/pharmacology ; Nucleus Accumbens/drug effects ; Nucleus Accumbens/metabolism ; Phencyclidine/pharmacology ; Picrotoxin/pharmacology ; Rats ; Rats, Wistar ; Receptors, Metabotropic Glutamate/metabolism
    Chemical Substances Excitatory Amino Acid Agonists ; Excitatory Amino Acid Antagonists ; GABA Antagonists ; Nicotinic Antagonists ; Receptors, Metabotropic Glutamate ; Picrotoxin (124-87-8) ; Dihydro-beta-Erythroidine (23255-54-1) ; N-Methylaspartate (6384-92-5) ; Phencyclidine (J1DOI7UV76) ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2017-02-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1948-7193
    ISSN (online) 1948-7193
    DOI 10.1021/acschemneuro.6b00397
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  7. Article ; Online: Disruption of latent inhibition by subchronic phencyclidine pretreatment in rats.

    Al-Ali, Asmaa M / Young, Andrew M J

    Behavioural brain research

    2019  Volume 368, Page(s) 111901

    Abstract: Repeated subchronic treatment with the NMDA-receptor antagonist, phencyclidine, causes behavioural changes in rats, which resemble cognitive and negative symptoms of schizophrenia. However, its effects on behaviours modelling positive symptoms are less ... ...

    Abstract Repeated subchronic treatment with the NMDA-receptor antagonist, phencyclidine, causes behavioural changes in rats, which resemble cognitive and negative symptoms of schizophrenia. However, its effects on behaviours modelling positive symptoms are less clear. This study investigated whether subchronic phencyclidine pretreatment affected latent inhibition: impaired conditioning following repeated preexposure of the to-be-conditioned stimulus. Female Lister-hooded rats were pretreated with phencyclidine or saline twice/day for 5 days, then remained drug-free for 10 days before latent inhibition testing. Saline pretreated animals showed latent inhibition, as expected. However, phencyclidine pretreated animals showed no latent inhibition: the effect of preexposure was attenuated, with no change in basic learning. Thus subchronic phencyclidine pretreatment does disrupt latent inhibition, and, importantly, this occurs after withdrawal from the drug, implicating changes in brain function enduring well beyond the time that the drug is present in the brain. In a separate task, discrimination of a novel object was significantly impaired by phencyclidine pretreatment confirming that five days of subchronic pretreatment was sufficient to invoke behavioural impairment previously reported after seven days pretreatment.
    MeSH term(s) Animals ; Behavior, Animal/drug effects ; Cognition/physiology ; Conditioning, Operant/drug effects ; Disease Models, Animal ; Female ; Memory/drug effects ; Motor Activity/drug effects ; Phencyclidine/pharmacology ; Rats ; Rats, Inbred Strains ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors ; Schizophrenia/physiopathology
    Chemical Substances Receptors, N-Methyl-D-Aspartate ; Phencyclidine (J1DOI7UV76)
    Language English
    Publishing date 2019-04-11
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 449927-x
    ISSN 1872-7549 ; 0166-4328
    ISSN (online) 1872-7549
    ISSN 0166-4328
    DOI 10.1016/j.bbr.2019.111901
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    Zs.A 1599: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  8. Article ; Online: Cortical Local Field Potential Power Is Associated with Behavioral Detection of Near-threshold Stimuli in the Rat Whisker System: Dissociation between Orbitofrontal and Somatosensory Cortices.

    Rickard, Rachel E / Young, Andrew M J / Gerdjikov, Todor V

    Journal of cognitive neuroscience

    2018  Volume 30, Issue 1, Page(s) 42–49

    Abstract: There is growing evidence that ongoing brain oscillations may represent a key regulator of attentional processes and as such may contribute to behavioral performance in psychophysical tasks. OFC appears to be involved in the top-down modulation of ... ...

    Abstract There is growing evidence that ongoing brain oscillations may represent a key regulator of attentional processes and as such may contribute to behavioral performance in psychophysical tasks. OFC appears to be involved in the top-down modulation of sensory processing; however, the specific contribution of ongoing OFC oscillations to perception has not been characterized. Here we used the rat whiskers as a model system to further characterize the relationship between cortical state and tactile detection. Head-fixed rats were trained to report the presence of a vibrotactile stimulus (frequency = 60 Hz, duration = 2 sec, deflection amplitude = 0.01-0.5 mm) applied to a single vibrissa. We calculated power spectra of local field potentials preceding the onset of near-threshold stimuli from microelectrodes chronically implanted in OFC and somatosensory cortex. We found a dissociation between slow oscillation power in the two regions in relation to detection probability: Higher OFC but not somatosensory delta power was associated with increased detection probability. Furthermore, coherence between OFC and barrel cortex was reduced preceding successful detection. Consistent with the role of OFC in attention, our results identify a cortical network whose activity is differentially modulated before successful tactile detection.
    MeSH term(s) Animals ; Brain Waves/physiology ; Electrodes, Implanted ; Frontal Lobe/physiology ; Male ; Models, Theoretical ; Rats, Sprague-Dawley ; Signal Detection, Psychological/physiology ; Signal Processing, Computer-Assisted ; Somatosensory Cortex/physiology ; Sulfonamides ; Thiadiazoles ; Touch Perception/physiology ; Vibration ; Vibrissae/physiology
    Chemical Substances 4-dodecyl-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide ; Sulfonamides ; Thiadiazoles
    Language English
    Publishing date 2018-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1007410-7
    ISSN 1530-8898 ; 0898-929X ; 1096-8857
    ISSN (online) 1530-8898
    ISSN 0898-929X ; 1096-8857
    DOI 10.1162/jocn_a_01187
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    Zs.A 2623: Show issues Location:
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  9. Article ; Online: Age-dependent effects of protein restriction on dopamine release.

    Naneix, Fabien / Peters, Kate Z / Young, Andrew M J / McCutcheon, James E

    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

    2020  Volume 46, Issue 2, Page(s) 394–403

    Abstract: Despite the essential role of protein intake for health and development, very little is known about the impact of protein restriction on neurobiological functions, especially at different stages of the lifespan. The dopamine system is a central actor in ... ...

    Abstract Despite the essential role of protein intake for health and development, very little is known about the impact of protein restriction on neurobiological functions, especially at different stages of the lifespan. The dopamine system is a central actor in the integration of food-related processes and is influenced by physiological state and food-related signals. Moreover, it is highly sensitive to dietary effects during early life periods such as adolescence due to its late maturation. In the present study, we investigated the impact of protein restriction either during adolescence or adulthood on the function of the mesolimbic (nucleus accumbens) and nigrostriatal (dorsal striatum) dopamine pathways using fast-scan cyclic voltammetry in rat brain slices. In the nucleus accumbens, protein restriction in adults increased dopamine release in response to low and high frequency trains of stimulation (1-20 Hz). By contrast, protein restriction during adolescence decreased nucleus accumbens dopamine release. In the dorsal striatum, protein restriction at adulthood has no impact on dopamine release but the same diet during adolescence induced a frequency-dependent increase in stimulated dopamine release. Taken together, our results highlight the sensitivity of the different dopamine pathways to the effect of protein restriction, as well as their vulnerability to deleterious diet effects at different life stages.
    MeSH term(s) Diet, Protein-Restricted ; Dopamine ; Electric Stimulation ; Nucleus Accumbens
    Chemical Substances Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2020-07-31
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639471-1
    ISSN 1740-634X ; 0893-133X
    ISSN (online) 1740-634X
    ISSN 0893-133X
    DOI 10.1038/s41386-020-0783-z
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    Zs.A 2379: Show issues Location:
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  10. Article ; Online: Synchronization in the prefrontal-striatal circuit tracks behavioural choice in a go-no-go task in rats.

    Stubbendorff, Christine / Molano-Mazon, Manuel / Young, Andrew M J / Gerdjikov, Todor V

    The European journal of neuroscience

    2018  Volume 49, Issue 5, Page(s) 701–711

    Abstract: Rodent striatum is involved in sensory-motor transformations and reward-related learning. Lesion studies suggest dorsolateral striatum, dorsomedial striatum and nucleus accumbens underlie stimulus-response transformations, goal-directed behaviour and ... ...

    Abstract Rodent striatum is involved in sensory-motor transformations and reward-related learning. Lesion studies suggest dorsolateral striatum, dorsomedial striatum and nucleus accumbens underlie stimulus-response transformations, goal-directed behaviour and reward expectation, respectively. In addition, prefrontal inputs likely control these functions. Here, we set out to study how reward-driven behaviour is mediated by the coordinated activity of these structures in the intact brain. We implemented a discrimination task requiring rats to either respond or suppress responding on a lever after the presentation of auditory cues in order to obtain rewards. Single unit activity in the striatal subregions and pre-limbic cortex was recorded using tetrode arrays. Striatal units showed strong onset responses to auditory cues paired with an opportunity to obtain reward. Cue-onset responses in both striatum and cortex were significantly modulated by previous errors suggesting a role of these structures in maintaining appropriate motivation or action selection during ongoing behaviour. Furthermore, failure to respond to the reward-paired tones was associated with higher pre-trial coherence among striatal subregions and between cortex and striatum suggesting a task-negative corticostriatal network whose activity may be suppressed to enable processing of reward-predictive cues. Our findings highlight that coordinated activity in a distributed network including both pre-limbic cortex and multiple striatal regions underlies reward-related decisions.
    MeSH term(s) Animals ; Auditory Perception/physiology ; Behavior, Animal/physiology ; Choice Behavior/physiology ; Corpus Striatum/physiology ; Discrimination, Psychological/physiology ; Electroencephalography Phase Synchronization ; Gyrus Cinguli/physiology ; Inhibition, Psychological ; Male ; Neurons/physiology ; Patch-Clamp Techniques ; Prefrontal Cortex/physiology ; Rats ; Reward
    Language English
    Publishing date 2018-04-02
    Publishing country France
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 645180-9
    ISSN 1460-9568 ; 0953-816X
    ISSN (online) 1460-9568
    ISSN 0953-816X
    DOI 10.1111/ejn.13905
    Database MEDical Literature Analysis and Retrieval System OnLINE

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