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  1. Article ; Online: Descriptive analysis to assess seasonal patterns of COVID-19 and influenza in low-income and middle-income countries in Asia, the Middle East and Latin America.

    Kyaw, Moe H / Spinardi, Julia Regazzini / Jagun, Oladayo / Franco Villalobos, Conrado / Kapetanakis, Venediktos / Sharf-Williams, Ruth / Yarnoff, Benjamin

    BMJ open

    2024  Volume 14, Issue 1, Page(s) e081019

    Abstract: Objectives: Understanding disease seasonality can help predict the occurrence of outbreaks and inform public health planning. Respiratory diseases typically follow seasonal patterns; however, knowledge regarding the seasonality of COVID-19 and its ... ...

    Abstract Objectives: Understanding disease seasonality can help predict the occurrence of outbreaks and inform public health planning. Respiratory diseases typically follow seasonal patterns; however, knowledge regarding the seasonality of COVID-19 and its impact on the seasonality of influenza remains limited. The objective of this study was to provide more evidence to understand the circulation of SARS-CoV-2, the virus responsible for COVID-19, in an endemic scenario to guide potential preventive strategies.
    Design: In this study, a descriptive analysis was undertaken to describe seasonality trends and/or overlap between COVID-19 and influenza in 12 low-income and middle-income countries using Our World in Data and FluMart data sources. Plots of COVID-19 and influenza cases were analysed.
    Setting: Singapore, Thailand, Malaysia, the Philippines, Argentina, Brazil, Mexico, South Africa, Morocco, Bahrain, Qatar and Saudi Arabia.
    Outcome measures: COVID-19 cases and influenza cases.
    Results: No seasonal patterns of SARS-CoV-2 or SARS-CoV-2/influenza cocirculation were observed in most countries, even when considering the avian influenza pandemic period.
    Conclusions: These results can inform public health strategies. The lack of observed seasonal behaviour highlights the importance of maintaining year-round vaccination rather than implementing seasonal campaigns. Further research investigating the influence of climate conditions, social behaviour and year-round preventive measures could be fundamental for shaping appropriate policies related to COVID-19 and respiratory viral disease control in low-income and middle-income countries as COVID-19 variant data and epidemiologic patterns accrue over time.
    MeSH term(s) Humans ; COVID-19/epidemiology ; Influenza, Human/epidemiology ; SARS-CoV-2 ; Seasons ; Latin America/epidemiology ; Developing Countries ; Middle East ; Thailand
    Language English
    Publishing date 2024-01-31
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2599832-8
    ISSN 2044-6055 ; 2044-6055
    ISSN (online) 2044-6055
    ISSN 2044-6055
    DOI 10.1136/bmjopen-2023-081019
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  2. Article: Blockade of muscarinic acetylcholine receptors in the ventral tegmental area disrupts food-related learning in rats.

    Sharf, Ruth / Ranaldi, Robert

    Psychopharmacology

    2006  Volume 184, Issue 1, Page(s) 87–94

    Abstract: Rationale: Stimulation of ventral tegmental area (VTA) muscarinic acetylcholine receptors (mAChRs) is implicated in feeding.: Objective: To investigate the effects of mAChR blockade in the VTA on food-related learning.: Methods: In experiment 1, ... ...

    Abstract Rationale: Stimulation of ventral tegmental area (VTA) muscarinic acetylcholine receptors (mAChRs) is implicated in feeding.
    Objective: To investigate the effects of mAChR blockade in the VTA on food-related learning.
    Methods: In experiment 1, rats (N=12) were placed in chambers containing food and received microinjections of 0 or 5 microg/0.5 microl scopolamine prior to the first four feeding sessions and the alternate dose prior to the tenth feeding session. In experiment 2 (N=9), the effects of daily microinjections of scopolamine on lever pressing under a progressive ratio schedule of food reinforcement were tested. In experiment 3 (N=34), the effects of daily microinjections of scopolamine on lever pressing maintained by conditioned reward were investigated.
    Results: In experiment 1, all rats demonstrated low consumption during session 1. However, pellet consumption for rats initially pretreated with the 0-microg dose rose to and stayed at maximal levels for the remaining sessions, even when pretreated with the 5-microg dose during the tenth session. Pellet consumption for rats initially pretreated with the 5-microg dose remained low, even for the first two sessions following the cessation of scopolamine pretreatment, and gradually rose to maximal levels by the eighth session. In experiment 2, scopolamine significantly decreased break points. In experiment 3, scopolamine failed to significantly decrease responding specifically on the lever producing the conditioned reward.
    Conclusions: Altogether, these data suggest that VTA mAChR stimulation is involved in feeding and food-related learning but may not be involved in responding maintained by conditioned reward.
    MeSH term(s) Animals ; Conditioning (Psychology)/drug effects ; Conditioning, Classical/drug effects ; Conditioning, Operant/drug effects ; Eating ; Feeding Behavior/drug effects ; Male ; Muscarinic Antagonists/pharmacology ; Rats ; Rats, Long-Evans ; Receptors, Muscarinic/metabolism ; Reinforcement Schedule ; Reward ; Scopolamine Hydrobromide/pharmacology ; Ventral Tegmental Area/drug effects ; Ventral Tegmental Area/metabolism
    Chemical Substances Muscarinic Antagonists ; Receptors, Muscarinic ; Scopolamine Hydrobromide (451IFR0GXB)
    Language English
    Publishing date 2006-01
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 130601-7
    ISSN 1432-2072 ; 0033-3158
    ISSN (online) 1432-2072
    ISSN 0033-3158
    DOI 10.1007/s00213-005-0235-9
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  3. Article ; Online: Role of orexin/hypocretin in dependence and addiction.

    Sharf, Ruth / Sarhan, Maysa / Dileone, Ralph J

    Brain research

    2009  Volume 1314, Page(s) 130–138

    Abstract: The orexins (or hypocretins) are hypothalamic neuropeptides that have been implicated in a variety of behaviors ranging from feeding to sleep and arousal. Evidence from animal models suggests a role for orexins in reward processing and drug addiction. In ...

    Abstract The orexins (or hypocretins) are hypothalamic neuropeptides that have been implicated in a variety of behaviors ranging from feeding to sleep and arousal. Evidence from animal models suggests a role for orexins in reward processing and drug addiction. In this review, we discuss orexin's interaction with the mesocorticolimbic reward pathway and the effects of drugs of abuse on the orexin system. We further review models of drug dependence and addiction and describe behavioral alterations that are seen when the orexin system is manipulated both pharmacologically and genetically. Based on the findings reported in the literature thus far, we posit that orexin functioning contributes to both drug reward and drug-related stress/aversive responsiveness; however, diverse anatomical substrates, and perhaps receptor specificity, contribute differentially to reward and stress components.
    MeSH term(s) Animals ; Humans ; Hypothalamic Area, Lateral/physiology ; Intracellular Signaling Peptides and Proteins/physiology ; Neural Pathways/drug effects ; Neural Pathways/physiology ; Neuropeptides/physiology ; Nucleus Accumbens/drug effects ; Nucleus Accumbens/physiology ; Orexins ; Reward ; Stress, Psychological/metabolism ; Stress, Psychological/physiopathology ; Substance Withdrawal Syndrome/metabolism ; Substance Withdrawal Syndrome/physiopathology ; Substance-Related Disorders/metabolism ; Substance-Related Disorders/physiopathology ; Ventral Tegmental Area/drug effects ; Ventral Tegmental Area/physiology
    Chemical Substances Intracellular Signaling Peptides and Proteins ; Neuropeptides ; Orexins
    Language English
    Publishing date 2009-08-20
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 1200-2
    ISSN 1872-6240 ; 0006-8993
    ISSN (online) 1872-6240
    ISSN 0006-8993
    DOI 10.1016/j.brainres.2009.08.028
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  4. Article ; Online: Orexin mediates the expression of precipitated morphine withdrawal and concurrent activation of the nucleus accumbens shell.

    Sharf, Ruth / Sarhan, Maysa / Dileone, Ralph J

    Biological psychiatry

    2008  Volume 64, Issue 3, Page(s) 175–183

    Abstract: Background: The lateral hypothalamic neuropeptide orexin (or hypocretin) is implicated in drug addiction. Although a role for orexin has been shown in reward and dependence, the molecular and neural mechanisms are unclear. We investigated the mechanism ... ...

    Abstract Background: The lateral hypothalamic neuropeptide orexin (or hypocretin) is implicated in drug addiction. Although a role for orexin has been shown in reward and dependence, the molecular and neural mechanisms are unclear. We investigated the mechanism and neuroanatomic basis of orexin's role in morphine withdrawal.
    Methods: C57BL/6J mice received chronic morphine followed by naloxone (0 or 1 mg/kg, subcutaneous) to precipitate withdrawal. Before naloxone, mice received SB-334867 (0 or 20 mg/kg, intraperitoneal), an orexin 1 receptor (Ox1r) antagonist. Using immunohistochemistry, c-Fos, a marker of cell activation, was quantified in the nucleus accumbens (Acb), lateral hypothalamus (LH), ventral tegmental area (VTA), and locus coeruleus (LC). Retrograde tracing with fluorogold (FG) was performed to determine whether orexin neurons project directly to the Acb.
    Results: SB-334867 before naloxone significantly attenuated withdrawal symptoms. Withdrawal was accompanied by an increase in c-Fos expression in the Acb shell (AcbSh), which was reduced by SB-334867 but had no effect on the VTA or the LC. Morphine withdrawal increased c-Fos expression in the dorsomedial (DMH) and perifornical (PFA) regions but not in the lateral region of the LH (LLH). Orexin neurons do not appear to form direct connections with Acb neurons.
    Conclusions: Altogether, these data demonstrate that orexin, acting via Ox1r, is critical for the expression of morphine withdrawal. AcbSh activation during withdrawal is dependent on Ox1r function and is likely mediated by indirect action of LH orexin neurons.
    MeSH term(s) Analysis of Variance ; Animals ; Benzoxazoles/pharmacology ; Intracellular Signaling Peptides and Proteins/metabolism ; Locus Coeruleus/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Morphine/administration & dosage ; Naloxone/therapeutic use ; Naphthyridines ; Narcotic Antagonists/therapeutic use ; Narcotics/administration & dosage ; Neuropeptides/metabolism ; Nucleus Accumbens/drug effects ; Nucleus Accumbens/metabolism ; Orexins ; Proto-Oncogene Proteins c-fos/metabolism ; Stilbamidines/metabolism ; Substance Withdrawal Syndrome/drug therapy ; Substance Withdrawal Syndrome/metabolism ; Substance Withdrawal Syndrome/pathology ; Urea/analogs & derivatives ; Urea/pharmacology ; Ventral Tegmental Area/drug effects ; Ventral Tegmental Area/metabolism
    Chemical Substances 1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea ; 2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt ; Benzoxazoles ; Intracellular Signaling Peptides and Proteins ; Naphthyridines ; Narcotic Antagonists ; Narcotics ; Neuropeptides ; Orexins ; Proto-Oncogene Proteins c-fos ; Stilbamidines ; Naloxone (36B82AMQ7N) ; Morphine (76I7G6D29C) ; Urea (8W8T17847W)
    Language English
    Publishing date 2008-04-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 209434-4
    ISSN 1873-2402 ; 0006-3223
    ISSN (online) 1873-2402
    ISSN 0006-3223
    DOI 10.1016/j.biopsych.2008.03.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Blockade of muscarinic acetylcholine receptors in the ventral tegmental area prevents acquisition of food-rewarded operant responding in rats.

    Sharf, Ruth / McKelvey, Jennifer / Ranaldi, Robert

    Psychopharmacology

    2006  Volume 186, Issue 1, Page(s) 113–121

    Abstract: Rationale: We recently found that muscarinic receptor (mAChR) stimulation in the ventral tegmental area (VTA) is involved in the acquisition of a feeding task.: Objective: To investigate the involvement of VTA mAChR and nicotinic receptors (nAChR) in ...

    Abstract Rationale: We recently found that muscarinic receptor (mAChR) stimulation in the ventral tegmental area (VTA) is involved in the acquisition of a feeding task.
    Objective: To investigate the involvement of VTA mAChR and nicotinic receptors (nAChR) in the acquisition and performance of a food-rewarded lever-pressing task.
    Methods: In experiment 1 (N=54), rats were trained under a fixed ratio 1 schedule of reinforcement and received bilateral intra-VTA microinjections of scopolamine (0, 2.5 or 5 microg/0.5 microl) or mecamylamine (0, 5 or 10 microg/0.5 microl) before each of the first four sessions. Before session 10, all rats that initially received a dose of either compound now received the vehicle and vice versa. In experiment 2 (N=14), rats were tested with scopolamine or mecamylamine while lever pressing under a progressive ratio schedule of reinforcement.
    Results: In experiment 1, lever pressing by rats initially treated with any mecamylamine dose or the scopolamine vehicle rose to and stayed at maximal levels for the remaining sessions. Responding by rats initially treated with the 2.5- or 5-microg dose of scopolamine remained low, even after the cessation of scopolamine treatment, and gradually rose to maximal levels by the final sessions. Injections of scopolamine 1 to 2 mm dorsal to the VTA had no significant effect on responding. In experiment 2, neither of the compounds significantly affected break points.
    Conclusions: Stimulation of VTA mAChR, but not of nAChR, is necessary for the acquisition of a food-rewarded lever-pressing task and neither is necessary for the performance of the task.
    MeSH term(s) Animals ; Conditioning, Operant/drug effects ; Food ; Male ; Mecamylamine/pharmacology ; Muscarinic Antagonists/pharmacology ; Nicotinic Antagonists/pharmacology ; Rats ; Rats, Long-Evans ; Reward ; Scopolamine Hydrobromide/pharmacology ; Ventral Tegmental Area/drug effects ; Ventral Tegmental Area/physiology
    Chemical Substances Muscarinic Antagonists ; Nicotinic Antagonists ; Scopolamine Hydrobromide (451IFR0GXB) ; Mecamylamine (6EE945D3OK)
    Language English
    Publishing date 2006-05
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 130601-7
    ISSN 1432-2072 ; 0033-3158
    ISSN (online) 1432-2072
    ISSN 0033-3158
    DOI 10.1007/s00213-006-0352-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Microinjections of SCH 23390 in the ventral tegmental area reduce operant responding under a progressive ratio schedule of food reinforcement in rats.

    Sharf, Ruth / Lee, David Y / Ranaldi, Robert

    Brain research

    2005  Volume 1033, Issue 2, Page(s) 179–185

    Abstract: We recently demonstrated that dopamine D1 receptors in the ventral tegmental area (VTA) are involved in intravenous cocaine reward. Here, we investigated whether VTA D1 receptors also are involved in food reward by testing the hypothesis that blockade of ...

    Abstract We recently demonstrated that dopamine D1 receptors in the ventral tegmental area (VTA) are involved in intravenous cocaine reward. Here, we investigated whether VTA D1 receptors also are involved in food reward by testing the hypothesis that blockade of dopamine D1 receptors in the VTA attenuates the rewarding effects of food. Eighteen rats, with bilateral cannulae positioned to allow for microinjections in or just dorsal to the VTA, were trained to lever press under a progressive ratio schedule of reinforcement. After stable break points (BPs) were established, the rats received bilateral microinjections of SCH 23390, a D1 receptor antagonist. In Experiment 1, where the reward consisted of 1 food pellet, injections of SCH 23390 (0, 1, 2, or 4 microg/0.5 microl) in the VTA (N=9) significantly decreased BPs (P <0.001), while bilateral microinjections dorsal to the VTA (N=9) did not. In Experiment 2 (N=6), where the reward consisted of 1 or 2 food pellets, intra-VTA injections of SCH 23390 (0 and 4 microg/0.5 microl) decreased BPs at the 1 food pellet level (P <0.05), but not at the 2 food pellet level. Thus, the data showed that intra-VTA microinjections of SCH 23390 reduced the rewarding effects of food. This effect was surmountable by increasing food reward, ruling out motoric effects, and did not occur when injections were made dorsal to VTA, eliminating the possibility that the effect was caused by the dorsal diffusion of drug. These data suggest that dendritically released dopamine in the VTA plays a significant role in food reward.
    MeSH term(s) Animals ; Benzazepines/administration & dosage ; Conditioning, Operant/drug effects ; Conditioning, Operant/physiology ; Dose-Response Relationship, Drug ; Eating/drug effects ; Eating/physiology ; Eating/psychology ; Male ; Microinjections/methods ; Rats ; Rats, Sprague-Dawley ; Reinforcement Schedule ; Ventral Tegmental Area/drug effects ; Ventral Tegmental Area/physiology
    Chemical Substances Benzazepines
    Language English
    Publishing date 2005-02-08
    Publishing country Netherlands
    Document type Comparative Study ; 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.2004.11.041
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  7. Article ; Online: Orexin mediates morphine place preference, but not morphine-induced hyperactivity or sensitization.

    Sharf, Ruth / Guarnieri, Douglas J / Taylor, Jane R / DiLeone, Ralph J

    Brain research

    2009  Volume 1317, Page(s) 24–32

    Abstract: Orexin (or hypocretin) has been implicated in mediating drug addiction and reward. Here, we investigated orexin's contribution to morphine-induced behavioral sensitization and place preference. Orexin-/- (OKO) mice and littermate wild-type (WT) controls ( ...

    Abstract Orexin (or hypocretin) has been implicated in mediating drug addiction and reward. Here, we investigated orexin's contribution to morphine-induced behavioral sensitization and place preference. Orexin-/- (OKO) mice and littermate wild-type (WT) controls (n=56) and C57BL/6J mice (n=67) were tested for chronic morphine-induced locomotor sensitization or for conditioned place preference (CPP) for a morphine- or a cocaine-paired environment. C57BL/6J mice received the orexin receptor 1 (Ox1r) antagonist, SB-334867, prior to test sessions. OKO mice did not significantly differ from WT controls in locomotor activity following acute- or chronic-morphine treatments. Similarly, mice treated with the Ox1r antagonist did not differ from vehicle controls in locomotor activity following acute- or chronic-morphine treatments. In contrast, while OKO mice did not differ from WT controls in preference for a morphine-paired environment, the Ox1r antagonist significantly attenuated place preference for a morphine-, but not a cocaine-paired, environment. These data suggest that orexin action is not required for locomotor responses to acute and chronic morphine, but Ox1r signaling can influence morphine-seeking in WT animals.
    MeSH term(s) Animals ; Benzoxazoles/administration & dosage ; Benzoxazoles/pharmacology ; Central Nervous System Agents/administration & dosage ; Central Nervous System Agents/pharmacology ; Cocaine/administration & dosage ; Cocaine/pharmacology ; Conditioning, Classical/drug effects ; Conditioning, Classical/physiology ; Dopamine Uptake Inhibitors/administration & dosage ; Dopamine Uptake Inhibitors/pharmacology ; Female ; Intracellular Signaling Peptides and Proteins/deficiency ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Morphine/administration & dosage ; Morphine/pharmacology ; Motor Activity/drug effects ; Motor Activity/physiology ; Mutation ; Naphthyridines ; Narcotics/administration & dosage ; Narcotics/pharmacology ; Neuropeptides/deficiency ; Neuropeptides/genetics ; Neuropeptides/metabolism ; Orexin Receptors ; Orexins ; Receptors, G-Protein-Coupled/antagonists & inhibitors ; Receptors, G-Protein-Coupled/metabolism ; Receptors, Neuropeptide/antagonists & inhibitors ; Receptors, Neuropeptide/metabolism ; Space Perception/drug effects ; Space Perception/physiology ; Time Factors ; Urea/administration & dosage ; Urea/analogs & derivatives ; Urea/pharmacology
    Chemical Substances 1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea ; Benzoxazoles ; Central Nervous System Agents ; Dopamine Uptake Inhibitors ; Intracellular Signaling Peptides and Proteins ; Naphthyridines ; Narcotics ; Neuropeptides ; Orexin Receptors ; Orexins ; Receptors, G-Protein-Coupled ; Receptors, Neuropeptide ; Morphine (76I7G6D29C) ; Urea (8W8T17847W) ; Cocaine (I5Y540LHVR)
    Language English
    Publishing date 2009-12-23
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; 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.2009.12.035
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  8. Article ; Online: Orexin signaling via the orexin 1 receptor mediates operant responding for food reinforcement.

    Sharf, Ruth / Sarhan, Maysa / Brayton, Catherine E / Guarnieri, Douglas J / Taylor, Jane R / DiLeone, Ralph J

    Biological psychiatry

    2010  Volume 67, Issue 8, Page(s) 753–760

    Abstract: Background: Orexin (hypocretin) signaling is implicated in drug addiction and reward, but its role in feeding and food-motivated behavior remains unclear.: Methods: We investigated orexin's contribution to food-reinforced instrumental responding ... ...

    Abstract Background: Orexin (hypocretin) signaling is implicated in drug addiction and reward, but its role in feeding and food-motivated behavior remains unclear.
    Methods: We investigated orexin's contribution to food-reinforced instrumental responding using an orexin 1 receptor (Ox1r) antagonist, orexin -/- (OKO) and littermate wildtype (WT) mice, and RNAi-mediated knockdown of orexin. C57BL/6J (n = 76) and OKO (n = 39) mice were trained to nose poke for food under a variable ratio schedule of reinforcement. After responding stabilized, a progressive ratio schedule was initiated to evaluate motivation to obtain food reinforcement.
    Results: Blockade of Ox1r in C57BL/6J mice impaired performance under both the variable ratio and progressive ratio schedules of reinforcement, indicating impaired motivational processes. In contrast, OKO mice initially demonstrated a delay in acquisition but eventually achieved levels of responding similar to those observed in WT animals. Moreover, OKO mice did not differ from WT mice under a progressive ratio schedule, indicating delayed learning processes but no motivational impairments. Considering the differences between pharmacologic blockade of Ox1r and the OKO mice, animals with RNAi mediated knockdown of orexin were then generated and analyzed to eliminate possible developmental effects of missing orexin. Orexin gene knockdown in the lateral hypothalamus in C57BL/6J mice resulted in blunted performance under both the variable ratio and progressive ratio schedules, resembling data obtained following Ox1r antagonism.
    Conclusions: The behavior seen in OKO mice likely reflects developmental compensation often seen in mutant animals. These data suggest that activation of the Ox1r is a necessary component of food-reinforced responding, motivation, or both in normal mice.
    MeSH term(s) Animals ; Benzoxazoles/pharmacology ; Conditioning, Operant/physiology ; Data Interpretation, Statistical ; Food ; Hypothalamic Area, Lateral/physiology ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity/drug effects ; Naphthyridines ; Neuropeptides/physiology ; Orexin Receptors ; Orexins ; RNA Interference ; Receptors, Neuropeptide/genetics ; Receptors, Neuropeptide/physiology ; Reinforcement Schedule ; Reinforcement, Psychology ; Urea/analogs & derivatives ; Urea/pharmacology ; Viruses/genetics
    Chemical Substances 1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea ; Benzoxazoles ; Hcrtr1 protein, mouse ; Intracellular Signaling Peptides and Proteins ; Naphthyridines ; Neuropeptides ; Orexin Receptors ; Orexins ; Receptors, Neuropeptide ; Urea (8W8T17847W)
    Language English
    Publishing date 2010-02-26
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 209434-4
    ISSN 1873-2402 ; 0006-3223
    ISSN (online) 1873-2402
    ISSN 0006-3223
    DOI 10.1016/j.biopsych.2009.12.035
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  9. Article ; Online: Regulation of nucleus accumbens activity by the hypothalamic neuropeptide melanin-concentrating hormone.

    Sears, Robert M / Liu, Rong-Jian / Narayanan, Nandakumar S / Sharf, Ruth / Yeckel, Mark F / Laubach, Mark / Aghajanian, George K / DiLeone, Ralph J

    The Journal of neuroscience : the official journal of the Society for Neuroscience

    2010  Volume 30, Issue 24, Page(s) 8263–8273

    Abstract: The lateral hypothalamus and the nucleus accumbens shell (AcbSh) are brain regions important for food intake. The AcbSh contains high levels of receptor for melanin-concentrating hormone (MCH), a lateral hypothalamic peptide critical for feeding and ... ...

    Abstract The lateral hypothalamus and the nucleus accumbens shell (AcbSh) are brain regions important for food intake. The AcbSh contains high levels of receptor for melanin-concentrating hormone (MCH), a lateral hypothalamic peptide critical for feeding and metabolism. MCH receptor (MCHR1) activation in the AcbSh increases food intake, while AcbSh MCHR1 blockade reduces feeding. Here biochemical and cellular mechanisms of MCH action in the rodent AcbSh are described. A reduction of phosphorylation of GluR1 at serine 845 (pSer(845)) is shown to occur after both pharmacological and genetic manipulations of MCHR1 activity. These changes depend upon signaling through G(i/o), and result in decreased surface expression of GluR1-containing AMPA receptors (AMPARs). Electrophysiological analysis of medium spiny neurons (MSNs) in the AcbSh revealed decreased amplitude of AMPAR-mediated synaptic events (mEPSCs) with MCH treatment. In addition, MCH suppressed action potential firing MSNs through K(+) channel activation. Finally, in vivo recordings confirmed that MCH reduces neuronal cell firing in the AcbSh in freely moving animals. The ability of MCH to reduce cell firing in the AcbSh is consistent with a general model from other pharmacological and electrophysiological studies whereby reduced AcbSh neuronal firing leads to food intake. The current work integrates the hypothalamus into this model, providing biochemical and cellular mechanisms whereby metabolic and limbic signals converge to regulate food intake.
    MeSH term(s) Action Potentials/drug effects ; Action Potentials/genetics ; Animals ; Barium Compounds/pharmacology ; Biotin/analogs & derivatives ; Biotin/metabolism ; Chlorides/pharmacology ; Dopamine and cAMP-Regulated Phosphoprotein 32/metabolism ; Dose-Response Relationship, Drug ; Enzyme Inhibitors/pharmacology ; Excitatory Postsynaptic Potentials/drug effects ; Excitatory Postsynaptic Potentials/physiology ; Gene Expression Regulation/drug effects ; Hypothalamic Hormones/genetics ; Hypothalamic Hormones/metabolism ; Hypothalamic Hormones/pharmacology ; Hypothalamus/cytology ; Hypothalamus/metabolism ; In Vitro Techniques ; Male ; Melanins/genetics ; Melanins/metabolism ; Melanins/pharmacology ; Mice ; Mice, Transgenic ; Neural Pathways/physiology ; Neurons/classification ; Neurons/cytology ; Neurons/drug effects ; Neurons/physiology ; Nucleus Accumbens/cytology ; Nucleus Accumbens/physiology ; Patch-Clamp Techniques/methods ; Pituitary Hormones/genetics ; Pituitary Hormones/metabolism ; Pituitary Hormones/pharmacology ; Potassium Channel Blockers/pharmacology ; Rats ; Rats, Long-Evans ; Rats, Wistar ; Receptors, AMPA/genetics ; Receptors, AMPA/metabolism ; Serine/metabolism ; Signal Transduction/drug effects ; Signal Transduction/physiology
    Chemical Substances Barium Compounds ; Chlorides ; Dopamine and cAMP-Regulated Phosphoprotein 32 ; Enzyme Inhibitors ; Hypothalamic Hormones ; Melanins ; Pituitary Hormones ; Potassium Channel Blockers ; Receptors, AMPA ; neurobiotin ; barium chloride (0VK51DA1T2) ; Serine (452VLY9402) ; melanin-concentrating hormone (67382-96-1) ; Biotin (6SO6U10H04) ; glutamate receptor ionotropic, AMPA 1 (TFZ3H25BS1)
    Language English
    Publishing date 2010-06-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 604637-x
    ISSN 1529-2401 ; 0270-6474
    ISSN (online) 1529-2401
    ISSN 0270-6474
    DOI 10.1523/JNEUROSCI.5858-09.2010
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  10. Article: Blockade of substantia nigra dopamine D1 receptors reduces intravenous cocaine reward in rats.

    Quinlan, Matthew G / Sharf, Ruth / Lee, David Y / Wise, Roy A / Ranaldi, Robert

    Psychopharmacology

    2004  Volume 175, Issue 1, Page(s) 53–59

    Abstract: Rationale: We have recently found that blockade of dopamine D1-type receptors in the ventral tegmental area reduces the rewarding effects of intravenous cocaine; here, we explored the possibility that blockade of D1 receptors in the adjacent substantia ... ...

    Abstract Rationale: We have recently found that blockade of dopamine D1-type receptors in the ventral tegmental area reduces the rewarding effects of intravenous cocaine; here, we explored the possibility that blockade of D1 receptors in the adjacent substantia nigra (SN)--not usually considered part of reward circuitry--might have similar effects.
    Objective: To test the hypothesis that blockade of dopamine D1 receptors in the SN reduces the rewarding effects of cocaine.
    Methods: Twenty one rats were prepared with intravenous catheters and with bilateral guide cannulae implanted such that injections could be made directly into the SN or just dorsal to the SN. The rats were trained to self-administer intravenous cocaine (1.0 mg/kg per injection) on a fixed-ratio 1 (FR1) schedule of reinforcement. After stable responding developed, 13 of the animals were tested following pretreatment with bilateral microinjections of SCH 23390 at doses of 0, 1, 2 or 4 microg/0.5 microl into the SN and 8 were tested with injections of 0 microg or 4 microg/0.5 microl into a site 2 mm dorsal to the SN site.
    Results: Microinjections of SCH 23390 in the SN significantly increased rates of cocaine self-administration, while injections dorsal to SN had no significant effect on responding.
    Conclusions: These data suggest that blockade of dendritically released DA in the SN reduces the rewarding effects of cocaine. These findings complement accumulating evidence that the rewarding effects of cocaine are not restricted to the drug's ability to elevate dopamine levels in the nucleus accumbens.
    MeSH term(s) Animals ; Benzazepines/pharmacology ; Central Nervous System Stimulants/administration & dosage ; Central Nervous System Stimulants/pharmacology ; Cocaine/administration & dosage ; Cocaine/pharmacology ; Cocaine-Related Disorders/psychology ; Dendrites/metabolism ; Dopamine/metabolism ; Dopamine Antagonists/pharmacology ; Injections, Intravenous ; Male ; Microinjections ; Rats ; Rats, Long-Evans ; Receptors, Dopamine D1/antagonists & inhibitors ; Receptors, Dopamine D1/physiology ; Reinforcement (Psychology) ; Reward ; Self Administration/psychology ; Substantia Nigra/drug effects ; Substantia Nigra/metabolism ; Time Factors
    Chemical Substances Benzazepines ; Central Nervous System Stimulants ; Dopamine Antagonists ; Receptors, Dopamine D1 ; Cocaine (I5Y540LHVR) ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2004-08
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 130601-7
    ISSN 1432-2072 ; 0033-3158
    ISSN (online) 1432-2072
    ISSN 0033-3158
    DOI 10.1007/s00213-003-1771-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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