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1.
iScience ; 27(5): 109724, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38711457

RESUMO

This work introduces a pioneering approach in the development of organic thin-film transistors (OTFTs), featuring a double-layer dielectric structure that combines poly(para-xylylene)s (Parylene) and poly(methyl methacrylate) (PMMA) to leverage the high insulation properties and high surface polarity of Parylene with the low insulation properties and low surface polarity of PMMA. This combination results in devices that showcase significantly enhanced electrical performance, including superior charge carrier mobility, increased current on/off ratios, and greater transconductance. Utilizing poly(3-hexylthiophene) (P3HT) for the active layer, the study demonstrates the advantage of the dual dielectric layers in minimizing hysteresis in the transfer curve, thereby facilitating the systematic growth of the organic active layer and enhancing electrical conductivity over single-layer alternatives. The superior performance of the Parylene/PMMA double-layer insulating structure opens new avenues for the advancement of organic electronics, presenting methodologies for performance optimization and expanding the application spectrum of OTFTs.

2.
Behav Brain Res ; 462: 114833, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38220059

RESUMO

Depression and anxiety are associated with dysfunction of the mesolimbic dopamine system. The rostromedial tegmental nucleus (RMTg) is predominantly composed of GABAergic neurons that exhibit dense projections and strongly inhibit mesolimbic dopaminergic neurons, proposed as a major "brake" for the system. Consequently, the RMTg may be a crucial brain region for regulating these emotions. The central cholinergic system, particularly the muscarinic receptors, plays an important regulatory role in depression and anxiety. M3 muscarinic receptors are distributed on GABAergic neurons in the RMTg, but their involvement in the regulation of depression and anxiety remains uncertain. This study aimed to examine the effects of RMTg M3 muscarinic receptors on regulating depression- and anxiety-like behaviors in adult male Wistar rats, as assessed through the forced swim, tail suspension, and elevated plus maze tests. The results showed that intra-RMTg injections of the M1/M3 muscarinic receptors agonist, pilocarpine (3, 10, and 30 µg/side), or the M3 muscarinic receptors antagonist, 4-DAMP (0.5, 1, and 2 µg/side), did not alter the immobility time in the forced swim and tail suspension tests. Additionally, pilocarpine (30 µg/side) decreased time spent in open arms and increased time in closed arms in the elevated plus maze; while 4-DAMP (1 and 2 µg/side) played the opposite role by increasing time spent in open arms and decreasing time in closed arms. These findings suggest that RMTg M3 muscarinic receptors have differential effects on regulating depression- and anxiety-like behaviors. Enhancing or inhibiting these receptors can produce anxiogenic or anxiolytic effects, but have no impact on depression-like behavior. Therefore, RMTg M3 muscarinic receptors are involved in regulating anxiety and may be a potential therapeutic target for anxiolytic drugs.


Assuntos
Pilocarpina , Piperidinas , Área Tegmentar Ventral , Ratos , Animais , Masculino , Pilocarpina/farmacologia , Depressão/tratamento farmacológico , Ratos Wistar , Receptores Muscarínicos , Ansiedade/tratamento farmacológico
3.
ACS Omega ; 8(40): 37248-37263, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37841127

RESUMO

A series of coal and gas outburst tests were conducted on coal seams in north China to determine the important order of gas pressure, in situ stress, and coal strength during coal and gas outbursts. And the typical phenomena of coal and gas outbursts were investigated. In addition, improved outburst energy equations were built to study the coal energy evolution process during coal and gas outbursts. The results show that the coal strength has the strongest influence on coal and gas outbursts, followed by the gas pressure and the in situ stress. The weights of pulverized coal with a particle size of less than 0.28 mm are consistent with the changing trend of the total weights of the pulverized coal particles in the corresponding outburst interval. Furthermore, the results suggest that the gas pressure monitored by the sensors close to the outburst hole begins to drop first and lasts for the longest time. The outburst coal presents obvious fracture and pulverization damage characteristics, and the pulverization damage features of the coal near the outburst hole are more obvious. In addition, the improved outburst energy equation was established, and the rationality of the improved outburst energy equation was verified by using the outburst orthogonal simulation experimental data and the on-site outburst accident cases. The results of this experiment have important guiding significance for preventing and controlling the occurrence of coal and gas outbursts and ensuring safe and efficient mining of coal mines.

4.
Carbohydr Polym ; 318: 121136, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37479427

RESUMO

Microbial growth and reproduction can cause food spoilage. Developing the controlled release packaging films for food is an ideal solution. In this study, polyethyleneimine (PEI) was grafted to cellulose nanofibers (CNF) films by Schiff base, and when the CNF/PEI films were stimulated by pH, PEI released from the CNF/PEI films due to Schiff base hydrolysis, improving the antibacterial efficiency of PEI. Stimulated by acid with pH of 4, the PEI cumulative release rate of the CNF/PEI800 and the CNF/PEI2000 films reached to 92.90 % and 87.28 %, respectively. At the same time, the amino groups of PEI protonated by obtaining H+, the charge density increased, and PEI molecular chains extended, enhancing the antibacterial activity of films. The Zeta potential value on the surface of the CNF/PEI film increased with the decrease of pH value. Schiff base synergized with protonation of PEI to achieve smart antibacteria of CNF packaging films. The antibacterial rates of the film against L. monocytogenes and E. coli were 94.7 % and 90.6 % at pH 4, but 29.5 % and 23.6 % at pH 8, respectively. The developed films also had good barrier properties of oxygen, visible light and mechanical properties, and had an attractive application prospect in food preservation to control release of antibacterial agent.


Assuntos
Escherichia coli , Polietilenoimina , Bases de Schiff , Embalagem de Produtos , Antibacterianos/farmacologia , Celulose
5.
Behav Brain Res ; 446: 114333, 2023 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-36764486

RESUMO

Social interaction is necessary for the development of individuals and society. Social interaction behaviors are rewarding. Similar to exogenous opioids, social interaction behaviors are able to induce rewarding effects that are regulated by the endogenous opioid system as well. As one type of opioid receptor, µ-opioid receptors (MORs), are densely expressed in the rostromedial tegmental nucleus (RMTg), which results in the RMTg being extremely sensitive to rewarding effects induced by exogenous and endogenous opioids. Here, we investigated how RMTg MORs played a role in rewarding effects induced by social interaction behaviors of male Wistar rats, using a conditioned place preference (CPP) model. Results showed that the CPP induced by social interaction behaviors was inhibited when the function of MORs was blocked via injecting CTAP (a selective MOR antagonist) intraperitoneally, and intra-RMTg injections of lower doses of CTAP affected the CPP in the same way. In addition, injecting CTAP intraperitoneally significantly inhibited the expression of pouncing behavior, while intra-RMTg injections of CTAP significantly inhibited the expression of all three types of social behaviors. These results suggest that RMTg MORs may be a crucial target and remain to be further explored in order to better understand the mechanism of the rewarding effects of social interaction behaviors.


Assuntos
Analgésicos Opioides , Interação Social , Ratos , Masculino , Animais , Analgésicos Opioides/farmacologia , Ratos Wistar , Tegmento Mesencefálico , Receptores Opioides/metabolismo , Receptores Opioides mu/metabolismo , Peptídeos Opioides/metabolismo
6.
Clin Transl Med ; 12(9): e1016, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36103390

RESUMO

BACKGROUND: To determine an appropriate dose of, and immunization schedule for, a vaccine SCoK against COVID-19 for an efficacy study; herein, we conducted randomized controlled trials to assess the immunogenicity and safety of this vaccine in adults. METHODS: These randomized, double-blind, placebo-controlled phase 1 and 2 trials of vaccine SCoK were conducted in Binhai District, Yan City, Jiangsu Province, China. Younger and older adult participants in phase 1 and 2 trials were sequentially recruited into different groups to be intramuscularly administered 20 or 40 µg vaccine SCoK or placebo. Participants were enrolled into our phase 1 and 2 studies to receive vaccine or placebo. RESULTS: No serious vaccine-related adverse events were observed in either trial. In both trials, local and systemic adverse reactions were absent or mild in most participants. In our phase 1 and 2 studies, the vaccine induced significantly increased neutralizing antibody responses to pseudovirus and live SARS-CoV-2. The vaccine induced significant neutralizing antibody responses to live SARS-CoV-2 on day 14 after the last immunization, with NT50s of 80.45 and 92.46 in participants receiving 20 and 40 µg doses, respectively; the seroconversion rates were 95.83% and 100%. The vaccine SCoK showed a similar safety and immunogenicity profiles in both younger participants and older participants. The vaccine showed better immunogenicity in phase 2 than in phase 1 clinical trial. Additionally, the incidence of adverse reactions decreased significantly in phase 2 clinical trial. The vaccine SCoK was well tolerated and immunogenic.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Idoso , Anticorpos Neutralizantes , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Método Duplo-Cego , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2
7.
Neurosci Lett ; 786: 136774, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-35809878

RESUMO

Opioid use disorder mainly results from functional defects in the brain reward loop, which includs the ventral tegmental area (VTA) and nucleus accumbens (NAc; consisting of shell and core, NAcS and NAcC). Reward effects contribute to opioid use disorder. RMTg M3 receptors play a role in opioid reward by regulating the γ-aminobutyric acid (GABA) neuron activity. Dopamine D1 receptors expressed on GABA neurons regulate opioid reward by mediating the dopamine neuron activity in the VTA. Therefore, we investigated the effect of activating M3 receptors by microinjecting pilocarpine into the RMTg along with activating D1 receptors by microinjecting SKF38393 into the VTA on morphine-induced reward effect, using the conditioned place preference (CPP) paradigm (locomotion was also recorded). We also investigated whether the activation of M3 receptors in the RMTg influenced dopamine release in the NAcS. The results showed that the inhibitory role of RMTg pilocarpine (60 µg/rat) infusions in morphine-induced CPP was reversed by VTA SKF38393 (4 µg/rat) infusions. Moreover, morphine (5 mg/kg, i.p.) increased dopamine release in the NAcS, which was blunted by microinjecting pilocarpine (60 µg/rat) into the RMTg. These results indicate that RMTg M3 receptors mediate morphine-induced reward effect, which is probably related to the dopamine activity within the VTA and NAcS. The relationship between RMTg M3 receptors and the mesolimbic dopamine system could be a potential direction for the treatment of opioid use disorder, but further verification through more comprehensive techniques is needed.


Assuntos
Morfina , Transtornos Relacionados ao Uso de Opioides , 2,3,4,5-Tetra-Hidro-7,8-Di-Hidroxi-1-Fenil-1H-3-Benzazepina/farmacologia , Analgésicos Opioides/farmacologia , Animais , Encéfalo , Colinérgicos/farmacologia , Dopamina/farmacologia , Neurônios Dopaminérgicos , Morfina/farmacologia , Núcleo Accumbens , Pilocarpina/farmacologia , Ratos , Receptores Muscarínicos , Recompensa , Área Tegmentar Ventral
8.
Psychopharmacology (Berl) ; 238(8): 2167-2177, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33834255

RESUMO

RATIONALE: Noradrenaline (NE) is closely related to attentive performance and impulsive control. However, the potential sex differences regarding attention and impulsivity under the noradrenergic modulation have been largely neglected. Therefore, our study aimed to investigate whether male and female rats exhibit differential responses to NE-related drugs during the five-choice serial reaction time task (5CSRT). METHODS: Male and female rats were trained in 5CSRT and administered with different NE drugs after obtaining stable baseline performance: atipamezole, a highly selective α2 receptor antagonist; prazosin, an α1 receptor antagonist; and atomoxetine, a selective NE reuptake inhibitor. Later, prazosin was selected to co-administration with atomoxetine. RESULTS: Male and female rats exhibited equal learning speed, and no significant baseline differences were found as measured by the 5CSRT. Atomoxetine decreased premature responses in both sexes, but the extent of this reduction was different, with the reduction greater in males. Besides, atomoxetine (1.8 mg/kg) increased the error of omissions in females. The high dose of prazosin (0.5 mg/kg) decreased the accuracy only in male rats, but this was ameliorated by the co-administration with atomoxetine. CONCLUSIONS: Atomoxetine showed significant improvement in impulsivity, but atomoxetine had less beneficial effects on impulsive control in females than in males, and it even impaired attentional performance in female rats. The α1 receptors were mainly responsible for NE drug-related sex differences in attention rather than impulsivity. The results obtained in this study indicate that the sex differences exist in both attention and impulsivity by the modulation of noradrenaline and raise the concern to improve sex-specific treatments.


Assuntos
Inibidores da Captação Adrenérgica/farmacologia , Atenção/efeitos dos fármacos , Atenção/fisiologia , Comportamento Impulsivo/efeitos dos fármacos , Comportamento Impulsivo/fisiologia , Caracteres Sexuais , Animais , Cloridrato de Atomoxetina/farmacologia , Feminino , Masculino , Norepinefrina/farmacologia , Ratos , Ratos Sprague-Dawley , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia
10.
Neurobiol Learn Mem ; 175: 107310, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32890758

RESUMO

Risk perception is an important factor that may mediate risk-based decision-making processes regulated by noradrenergic (NA) and serotonergic (5-HT) systems. Most risk-based decision-making models involve complex factors, such as risk perception or reward value, such that the final decision is the result of the interactions among these factors. However, the contribution of risk perception per se in risk decisions has remained unclear. Therefore, in the present study, we made some modifications to the classical probabilistic discounting task (PDT) to focus on the impact of risk perception and noradrenergic/serotonergic systems on decision-making behavior. Meanwhile, we conducted an elevated plus-maze (EPM) test to detect the correlation between anxiety and choice behavior. In the current study, rats had to choose between a "certain" lever that delivered a certain number of pellets and a "risky" lever that delivered eight pellets in a probabilistic manner (descending: 50%, 25%, 12.5% or ascending 12.5%, 25%, 50% of the time). The long-term rewarding values of the two levers were always identical in each block within each session. According to their baseline performances in choosing the risky lever, rats were divided into the risk-prefer group and risk-averse group. The results showed that there was a significant correlation between open arm time in EPM and risky choice for both descending order and ascending order, indicating that highly anxious rats more often preferred the safe option under risk. Pharmacological stimulation of α2-adrenergic receptors via dexmedetomidine (0.01 mg/kg) decreased the preference of probabilistic rewards in the risk-prefer group, while blocking α2 receptors by atipamezole (0.3 mg/kg) also reduced risky choices. The NA reuptake inhibitor, atomoxetine, increased the preference for risky choices in the risk-prefer group, the effect of which was attained via multiple superimposed doses. Administration of the 5-HT2A receptor agonist, DOI (0.1 mg/kg), increased risk-taking behavior in the risk-prefer group. Taken together, these results suggest that NA may be more inclined to process negative information such as loss or uncertainty in the regulation of risk-related decision making, whereas 5-HT may function primarily to increase risk-taking behavior. Our findings may help to further elucidate how noradrenergic and serotonergic systems differentially affect individuals with different risk preferences in terms of regulating risk perception in risk-related decision making.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Tomada de Decisões/efeitos dos fármacos , Recompensa , Assunção de Riscos , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Anfetaminas/farmacologia , Animais , Tomada de Decisões/fisiologia , Dexmedetomidina/farmacologia , Imidazóis/farmacologia , Ratos , Medição de Risco
11.
Eur J Pharmacol ; 882: 173274, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32534071

RESUMO

Opioids strongly inhibit GABAergic neurons in the rostromedial tegmental nucleus (RMTg) that expresses µ-opioid receptors to induce rewarding and psychomotor effects. M3 and M4 muscarinic receptors are co-localized with µ-opioid receptors at these GABAergic neurons. This study explored whether RMTg M3 and M4 muscarinic receptors are involved in regulating opioid-induced reward and locomotion via a conditioned place preference (CPP) paradigm. Selective muscarinic receptor agonists and antagonists were both singly and combinatorically injected into the RMTg to examine their effects on the acquisition of systemic morphine-induced CPP and locomotor activity. The M3 muscarinic receptor agonist, pilocarpine, inhibited the acquisition of morphine-induced CPP, whereas its antagonist, 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP, 1 µg/side), reversed the inhibitory effect of pilocarpine (30 µg/side). Additionally, 4-DAMP increased locomotor activity while pilocarpine (30 µg/side) partially decreased locomotor activity when combined with morphine. In contrast, the M4 muscarinic receptor agonist, LY2033298 (0.1 and 0.2 µg/side), and antagonist, tropicamide (20 and 40 µM/side), did not affect the acquisition of morphine-induced CPP or locomotor activity. Taken together, our findings suggest that RMTg M3 muscarinic receptors are involved in opioid-induced rewarding and psychomotor effects. Therefore, RMTg M3 muscarinic receptors may represent a promising target for the treatment of opioid addiction.


Assuntos
Condicionamento Psicológico , Receptor Muscarínico M3/metabolismo , Recompensa , Tegmento Mesencefálico/metabolismo , Analgésicos Opioides , Animais , Locomoção/efeitos dos fármacos , Masculino , Morfina , Agonistas Muscarínicos/farmacologia , Antagonistas Muscarínicos/farmacologia , Ratos Wistar , Receptor Muscarínico M3/agonistas , Receptor Muscarínico M3/antagonistas & inibidores , Receptor Muscarínico M4/agonistas , Receptor Muscarínico M4/antagonistas & inibidores , Receptor Muscarínico M4/metabolismo
12.
Pharmacol Biochem Behav ; 176: 43-52, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30444985

RESUMO

The non-selective muscarinic receptor agonist oxotremorine-M has been found to decrease impulsive choice in high-impulsive (HI) rats and increase impulsive choice in low-impulsive (LI) rats, but little is known about the muscarinic M1 receptor agonist N-desmethylclozapine (NDMC). This study investigated effects of NDMC on impulsive choice, and the effect of co-administration of NDMC with the dopamine D1-like receptor antagonist SCH 23390 or D2-like receptor antagonist raclopride on impulsive choice in HI and LI rats, characterized by basal levels of impulsive choice in a delay-discounting task. The results revealed that NDMC (1 and 2 mg/kg) significantly increased impulsive choice in HI, but not LI rats. SCH 23390 significantly promoted impulsive choice in HI rats at 0.01 mg/kg, and in LI rats at 0.0075 and 0.01 mg/kg. Moreover, SCH 23390 (0.005 and 0.0075 mg/kg) significantly inhibited the increase in impulsive choice induced by NDMC (1 mg/kg) in HI rats, whereas the increase in impulsive choice produced by SCH 23390 (0.0075 mg/kg) was significantly reversed by NDMC (1 mg/kg) in LI rats. Raclopride (0.04, 0.08, and 0.12 mg/kg) did not affect choice in both HI and LI rats, but significantly antagonized the increase in impulsive choice induced by NDMC (1 mg/kg) in HI rats. These findings suggest that D1- and D2-like receptors might be involved in different effects of the M1 receptor agonist on impulsive choice between HI and LI rats.


Assuntos
Comportamento Impulsivo/fisiologia , Receptor Muscarínico M1/fisiologia , Receptores de Dopamina D1/fisiologia , Receptores de Dopamina D2/fisiologia , Análise de Variância , Animais , Área Sob a Curva , Comportamento Animal/efeitos dos fármacos , Benzazepinas/administração & dosagem , Benzazepinas/farmacologia , Clozapina/administração & dosagem , Clozapina/análogos & derivados , Clozapina/farmacologia , Desvalorização pelo Atraso/efeitos dos fármacos , Desvalorização pelo Atraso/fisiologia , Antagonistas dos Receptores de Dopamina D2/administração & dosagem , Antagonistas dos Receptores de Dopamina D2/farmacologia , Comportamento Impulsivo/efeitos dos fármacos , Masculino , Racloprida/administração & dosagem , Racloprida/farmacologia , Ratos , Ratos Sprague-Dawley , Receptor Muscarínico M1/agonistas , Receptores de Dopamina D1/antagonistas & inibidores
13.
Behav Brain Res ; 360: 128-133, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30529589

RESUMO

Repeated administration of morphine profoundly influences the dopaminergic and cholinergic systems in the nucleus accumbens [including the shell of the nucleus accumbens (NAcS)]. Further, dopamine release is regulated by the cholinergic system, especially the M4 receptor. Drug priming is one of the main factors that induces relapse in drug addiction. The present study first investigated how activation of the M4 receptor in the NAcS affects the expression of morphine-induced behavioral sensitization, through the administration of an M4 agonist (LY2033298) and antagonist (tropicamide), as well as a combination of an acetylcholinesterase inhibitor and M4 antagonist (huperzine-A + tropicamide). Additionally, the influence of a dopamine receptor agonist, in conjunction with an M4 agonist (i.e., SKF38393 + LY2033298), was also examined. Behavioral sensitization was established by exposure to 5 mg/kg morphine once every three days for a total of three exposures. The expression of behavioral sensitization was challenged by 5 mg/kg morphine. Results showed that (1) microinjection of the M4 receptor agonist LY2033298 (0.2 µg/side), but not the antagonist tropicamide (5, 10, or 20 µM/side) into the NAcS blocked the expression of behavioral sensitization; (2) tropicamide (20 µM/side) reversed the inhibition effect of huperzine-A on this behavior; and (3) SKF38393 (1 µg/side) reversed the inhibitory effect of LY2033298 on the expression of morphine-induced behavioral sensitization. These results suggest that the cholinergic M4 receptor in the NAcS plays an important role in the morphine-induced expression of behavioral sensitization through the regulation of dopamine function in rats.


Assuntos
Sintomas Comportamentais/induzido quimicamente , Dopamina/metabolismo , Morfina/efeitos adversos , Entorpecentes/efeitos adversos , Núcleo Accumbens/efeitos dos fármacos , Receptor Muscarínico M4/metabolismo , 2,3,4,5-Tetra-Hidro-7,8-Di-Hidroxi-1-Fenil-1H-3-Benzazepina/farmacologia , Animais , Antipsicóticos/farmacologia , Agonistas de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Locomoção/efeitos dos fármacos , Masculino , Microinjeções , Antagonistas Muscarínicos/farmacologia , Ácidos Nicotínicos/farmacologia , Ratos , Ratos Wistar , Tiofenos/farmacologia , Tropicamida/farmacologia
14.
Eur J Pharmacol ; 841: 57-66, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30268663

RESUMO

Center arena activity in open field (OF) test is associated with risk-taking behaviors. Noradrenaline and serotonin (5-HT) are neurotransmitters involved in both center arena activity and risk-based decision-making. However, the effects of noradrenergic/serotonergic systems on risk-based decision-making in rats with different center arena activity levels have not been clearly characterized. In this study, we explored the effects of the noradrenergic and serotonergic systems on risk-based decision-making in long center-time (LCT group) and short center-time (SCT group) rats. The two groups were formed based on performance in OF test. Then we tested their risk-based decision-making using probability discounting task (PDT); rats had to choose between "small/certain" lever that always delivered one pellet and "large/risky" lever that delivered four pellets in a probabilistic manner (100%, 50%, 25%, 12.5%). The results showed the SCT group chose the large/risky lever less often in 12.5% block and were more sensitive to loss than the SCT group. α2-adrenergic receptor agonist dexmedetomidine (0.01 mg/kg) decreased the frequency of risky choice, while the noradrenaline reuptake inhibitor (NRI) reboxetine (10 mg/kg) had the opposite effect only in the SCT group. Serotonin-noradrenaline reuptake inhibitor (SNRI) duloxetine (5 mg/kg) decreased preference for the large/risky option only in the SCT group. In contrast, pharmacological manipulations of the serotonin system did not affect the frequency of risky choices. These results suggest that noradrenergic system may be involved in weighing gains and losses for probabilistic discounting. Our findings also provide a better understanding of the involvement of center arena activity in risk-taking.


Assuntos
Tomada de Decisões , Norepinefrina/metabolismo , Assunção de Riscos , Serotonina/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento de Escolha/efeitos dos fármacos , Citalopram/farmacologia , Tomada de Decisões/efeitos dos fármacos , Dexmedetomidina/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley , Reboxetina/farmacologia , Recompensa
15.
Sci Rep ; 8(1): 3260, 2018 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-29459749

RESUMO

The analysis of status and major sources of human pressures on natural reserves (NRs) is important for optimizing their management. This study selected population density, gross domestic product (GDP) density and areal percentage of human land use to reveal the human pressures of national and provincial NRs (NNRs and PNRs) in Yunnan Province, China. We calculated three types of internal and external human pressure index (HPI) and comprehensive HPI (CHPI) for NRs. Human pressures on most of NRs were slight and light, indicating that most of NRs were well protected. Human pressures on PNRs were higher than on NNRs; with respect to five types of NRs, geological relict NRs were facing the highest human pressures, followed by wetland ecosystem NRs. Land use and population density were the main human pressures on these NRs. Yunnan Province should put the highest emphasis on three NNRs and two Ramsar site PNRs with severe CHPI, secondly pay attention to eight conservation-oriented PNRs with extreme or severe CHPI. It's urgent for Yunnan to implement scientific policies and measures to reduce land use and population density pressures of NRs, especially with severe and extreme CHPI, by transforming internal land use and/or implementing residents' eco-migration.


Assuntos
Conservação dos Recursos Naturais/métodos , Atividades Humanas , Recursos Naturais , China , Geografia , Produto Interno Bruto , Humanos , Densidade Demográfica
16.
Eur J Pharmacol ; 819: 51-57, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29196177

RESUMO

Both drug-related cues and drug priming are the main factors that induce relapse of drug addiction. Previous research has reported that blockade of the muscarinic receptors could significantly depress addictive behavior, suggesting that the muscarinic receptors might be involved in drug use and relapse behavior. The nucleus accumbens (NAc), especially the shell of the NAc, where the muscarinic receptors are expressed, is critical for craving and relapse. This study investigated the effects of microinfusion of the muscarinic receptor antagonist scopolamine into the NAc shell on context- and morphine-induced expression of behavioral sensitization. Behavioral sensitization was established by exposure to 5mg/kg morphine once daily for five consecutive days. Expression of behavioral sensitization was induced by saline challenge or 5mg/kg morphine challenge. The results showed that: (a) the muscarinic receptor antagonist scopolamine (10.8µg/rat) microinjected into the NAc shell blocked expression of conditional sensitization; (b) acetylcholinesterase inhibitor huperzine-A (0.5 and 0.1µg/rat), but not scopolamine (10.8µg/rat), microinjected into the NAc shell blocked morphine-induced expression of sensitization; and (c) pre-infusion of scopolamine (10.8µg/rat) reversed the inhibitory effect of huperzine-A (0.5µg/rat) on morphine-induced sensitization. Our findings suggest that muscarinic receptors in the NAc shell play different roles in context-induced and morphine-challenged expression of behavioral sensitization.


Assuntos
Comportamento Animal/efeitos dos fármacos , Morfina/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Receptores Muscarínicos/metabolismo , Alcaloides/farmacologia , Animais , Masculino , Núcleo Accumbens/fisiologia , Ratos , Ratos Wistar , Escopolamina/farmacologia , Sesquiterpenos/farmacologia
17.
Pharmacol Biochem Behav ; 160: 39-46, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28807620

RESUMO

Background and Aim The cholinergic system can affect drug reward. The present study aimed to examine the roles of muscarinic acetylcholine receptor (mAChR) and nicotinic acetylcholine receptor (nAChR) in morphine-induced behavioral sensitization. METHODS: To analyze the roles of mAChR and nAChR in behavioral sensitization induced by morphine (5mg/kg), seven experiments were designed. Experiments 1 and 2 examined the effects of 3, 1, and 0.3 mg/kg scopolamine and 0.2, 0.1, and 0.05mg/kg scopolamine, respectively, on the locomotor activity when administered alone. Experiments 3 and 4 explored the effect of scopolamine on morphine-induced behavioral sensitization. Experiment 5 studied the effect of mecamylamine on morphine-induced behavioral sensitization. Experiments 6 and 7 investigated the effects of scopolamine+huperzine A and mecamylamine+huperzine A, respectively, on morphine-induced behavioral sensitization. RESULTS: The results revealed that 3mg/kg scopolamine, which significantly enhanced locomotor activity when administered alone, inhibited the acquisition of morphine-induced sensitization. However, mecamylamine (0.5, 1, 2mg/kg) did not have these effects. The co-administration of scopolamine (0.05 mg/kg)+huperzine A (0.4mg/kg) or mecamylamine (1mg/kg)+huperzine A (0.4mg/kg) did not affect the acquisition of morphine-induced behavioral sensitization. Scopolamine (0.05mg/kg) which did not affect the locomotor activity when administered alone, but not mecamylamine (1mg/kg), reversed the acute attenuation effect of huperzine A (0.4mg/kg) on morphine-induced locomotor activity at the acquisition stage and reversed the inhibition of huperzine A on the expression of morphine-induced sensitization. CONCLUSION: The mAChR might play a more important role in morphine-induced locomotor activity and the expression of morphine-induced behavioral sensitization. The mechanisms of mAChR and nAChR were relatively separate in morphine-induced sensitization.


Assuntos
Comportamento Animal/efeitos dos fármacos , Morfina/farmacologia , Receptores Muscarínicos/fisiologia , Alcaloides/farmacologia , Animais , Relação Dose-Resposta a Droga , Locomoção/efeitos dos fármacos , Masculino , Mecamilamina/farmacologia , Ratos , Ratos Wistar , Receptores Nicotínicos/fisiologia , Escopolamina/farmacologia , Sesquiterpenos/farmacologia
18.
Exp Ther Med ; 13(4): 1584-1591, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28413513

RESUMO

Acetylcholinesterase inhibitors are regarded as promising therapeutic agents to treat addiction. The current study aimed to examine the effects of huperzine A, a cholinesterase inhibitor, on behavioral sensitization induced by repeated morphine administration and relapse induced by contextual conditioning. The present study also assessed whether the state-dependency hypothesis may explain the results. Adult rats were divided into four groups (n=8) and intraperitoneally injected with 0.2, 0.3 or 0.4 mg/kg huperzine A or saline (1 ml/kg, control), for 5 days. The effect of repeated huperzine A administration alone on locomotor activity was assessed. For the experiments that analyzed the development of morphine-induced sensitization, 40 rats were divided into five groups (n=8): Saline+Saline, Saline+Morphine, 0.2, 0.3 and 0.4 mg/kg huperzine A+Morphine. Following a withdrawal period of 7 days, all animals were administered saline or morphine, as appropriate. To test the state-dependency hypothesis, the rats in the Saline+Morphine group were injected with saline and morphine, while the other three groups were administered different doses of huperzine A and morphine. To examine the effect of huperzine A on the expression of morphine-induced sensitization, the rats in huperzine A+Morphine groups were injected with appropriate concentrations of huperzine A, and morphine. The current results indicated that the administration of huperzine A alone did not affect locomotor activity, while higher doses of huperzine A inhibited the addictive behavior induced by morphine at the development phase. Additionally, huperzine A administration during the expression phase of morphine sensitization did not inhibit the relapse induced by administration of saline. Furthermore, 0.4 mg/kg huperzine A inhibited the expression of morphine-induced behavioral sensitization. Therefore, the results of the current study do not support the state-dependency hypothesis.

19.
Behav Processes ; 138: 127-133, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28279781

RESUMO

Impulsivity is an important personality trait that affects people's lives every day. Because of the complicated structures and various measurements of impulsivity, the conclusion that whether there were gender differences on impulsivity remained controversial. In our study, we used delay discounting and probability discounting to measure impulsive choice and employed stop signal reaction time task (SSRT) to measure impulsive action within the same subjects. No inherent gender differences were found, either on impulsive choice or on impulsive action. However, after adding a working memory (WM) task, we found an interaction between gender and WM: males made more impulsive choices in the delay discounting task, but females remained no change, and this only occurred when the reward amount was large; in the SSRT, the males showed better inhibitory control under the WM load condition, but females did not. These results demonstrate that gender difference does not exist on impulsivity biologically, but the increased working memory load could affect the gender's sense of delay gratification and the ability of inhibitory control differently. These findings can contribute to the studies of gender differences on impulsivity and draw attention to the need for further research that gender factors should be considered more carefully when exploring the effects of working memory.


Assuntos
Comportamento Impulsivo , Memória de Curto Prazo , Caracteres Sexuais , Adulto , Comportamento de Escolha , Desvalorização pelo Atraso , Feminino , Humanos , Masculino , Tempo de Reação , Recompensa , Adulto Jovem
20.
Pharmacol Biochem Behav ; 142: 56-63, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26772787

RESUMO

The effect of acetylcholine on impulsive choice is thought to be due to interactions between cholinergic and dopaminergic systems, but this hypothesis has not been proven. This study investigated whether D1-like receptors were involved in the effects of the muscarinic cholinergic agonist oxotremorine on impulsive choice in high-impulsive rats (HI rats, n=8) and low-impulsive rats (LI rats, n=8) characterized by basal levels of impulsive choice in a delay-discounting task. The results revealed that oxotremorine (0.05mg/kg) significantly increased the choice of the large reinforcer in HI rats, whereas decreased the choice of the large reinforcer in LI rats. The D1-like antagonist SCH 23390 produced significant reductions in the large-reinforcer choice in HI rats (0.01mg/kg) and LI rats (0.005, 0.0075, and 0.01mg/kg). SCH 23390 significantly inhibited the increase in the choice of the large reinforcer induced by oxotremorine (0.05mg/kg) in HI rats at doses of 0.005 and 0.0075mg/kg, but enhanced the effect of oxotremorine in LI rats only at the dose of 0.0075mg/kg. These findings suggested that D1-like receptors might be involved in the differential effects of oxotremorine on impulsive choice between HI rats and LI rats.


Assuntos
Benzazepinas/administração & dosagem , Comportamento de Escolha/efeitos dos fármacos , Comportamento Impulsivo/efeitos dos fármacos , Agonistas Muscarínicos/administração & dosagem , Oxotremorina/administração & dosagem , Animais , Relação Dose-Resposta a Droga , Ratos
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