scholarly journals Preclinical Determinants of Drug Choice under Concurrent Schedules of Drug Self-Administration

2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
Matthew L. Banks ◽  
S. Stevens Negus
Keyword(s):  
Experimental Analysis ◽  
Critical Role ◽  
Concurrent Schedules ◽  
Self Administration ◽  
Future Directions ◽  
Drug Choice ◽  
Choice Procedures ◽  
Stimulus Effects ◽  
Biological Determinants ◽  
Reinforcing Effects

Drug self-administration procedures have played a critical role in the experimental analysis of psychoactive compounds, such as cocaine, for over 50 years. While there are numerous permutations of this procedure, this paper will specifically focus on choice procedures using concurrent schedules of intravenous drug self-administration. The aims of this paper are to first highlight the evolution of drug choice procedures and then review the subsequent preclinical body of literature utilizing these choice procedures to understand the environmental, pharmacological, and biological determinants of the reinforcing stimulus effects of drugs. A main rationale for this paper is our proposition that choice schedules are underutilized in investigating the reinforcing effects of drugs in assays of drug self-administration. Moreover, we will conclude with potential future directions and unexplored scientific space for the use of drug choice procedures.

scholarly journals Small Molecule Inhibitors of Influenza Virus Entry

2021 ◽  
Vol 14 (6) ◽  
pp. 587
Author(s):  
Zhaoyu Chen ◽  
Qinghua Cui ◽  
Michael Caffrey ◽  
Lijun Rong ◽  
Ruikun Du
Keyword(s):  
Influenza Virus ◽  
Membrane Fusion ◽  
Small Molecule ◽  
Drug Target ◽  
Small Molecule Inhibitors ◽  
Virus Entry ◽  
Critical Role ◽  
Structural Basis ◽  
Future Directions ◽  
The Past

Hemagglutinin (HA) plays a critical role during influenza virus receptor binding and subsequent membrane fusion process, thus HA has become a promising drug target. For the past several decades, we and other researchers have discovered a series of HA inhibitors mainly targeting its fusion machinery. In this review, we summarize the advances in HA-targeted development of small molecule inhibitors. Moreover, we discuss the structural basis and mode of action of these inhibitors, and speculate upon future directions toward more potent inhibitors of membrane fusion and potential anti-influenza drugs.

scholarly journals Impact of Morphine Dependence and Withdrawal on the Reinforcing Effectiveness of Fentanyl, Cocaine, and Methamphetamine in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Robert W. Seaman Jr ◽  
Gregory T. Collins
Keyword(s):  
Opioid Dependence ◽  
Progressive Ratio ◽  
Morphine Dependence ◽  
Sprague Dawley ◽  
Self Administration ◽  
Stimulant Use ◽  
Concurrent Use ◽  
Reinforcing Effects ◽  
The Individual ◽  
The Impact

Recent estimates suggest increased popularity of the concurrent use of opioids and stimulants, with over 50% of treatment-seeking opioid users reporting regular stimulant use. The goal of the current study was to determine how opioid dependence and withdrawal affect the reinforcing effects of fentanyl, cocaine, and methamphetamine. Male Sprague-Dawley rats were allowed to self-administer fentanyl under a progressive ratio (PR) schedule of reinforcement. Baseline evaluations of reinforcing effectiveness of fentanyl, cocaine, and methamphetamine were determined. Opioid dependence was then established by administering escalating doses of morphine (10–40 mg/kg) twice-daily for four days and subsequently maintained by once-daily injections of 40 mg/kg morphine. To evaluate the impact of opioid dependence and withdrawal on the self-administration of fentanyl, cocaine, and methamphetamine, sessions occurred either 12 or 20 h after the morphine, respectively. During opioid withdrawal, the fentanyl dose-response curve was shifted rightward with an increase in maximal effectiveness, whereas it was shifted rightward with a reduction in maximal effectiveness when evaluated in rats currently dependent on opioids, relative to baseline. The reinforcing effects of cocaine and methamphetamine were unchanged by either condition. The current studies provide direct evidence that the reinforcing effects of fentanyl are increased in opioid-withdrawn rats and reduced in opioid-dependent rats, relative to rats that are not physically dependent on opioids. These findings suggest that motivations to use opioids are dependent on the state of the individual whereas stimulants retain their reinforcing effects regardless of whether the individual is in an opioid-dependent or withdrawn state.

scholarly journals MicroRNA in Pancreatic Cancer: From Biology to Therapeutic Potential

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 752 ◽  
Author(s):  
Rawat ◽  
Kadian ◽  
Gupta ◽  
Kumar ◽  
Chain ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Mirna Biogenesis ◽  
Effective Management ◽  
Future Directions ◽  
Novel Therapeutic Strategies ◽  
Conclusion Section

Pancreatic cancer is one of the most aggressive malignancies, accounting for more than 45,750 deaths annually in the U.S. alone. The aggressive nature and late diagnosis of pancreatic cancer, coupled with the limitations of existing chemotherapy, present the pressing need for the development of novel therapeutic strategies. Recent reports have demonstrated a critical role of microRNAs (miRNAs) in the initiation, progression, and metastasis of cancer. Furthermore, aberrant expressions of miRNAs have often been associated with the cause and consequence of pancreatic cancer, emphasizing the possible use of miRNAs in the effective management of pancreatic cancer patients. In this review, we provide a brief overview of miRNA biogenesis and its role in fundamental cellular process and miRNA studies in pancreatic cancer patients and animal models. Subsequent sections narrate the role of miRNA in, (i) cell cycle and proliferation; (ii) apoptosis; (iii) invasions and metastasis; and (iv) various cellular signaling pathways. We also describe the role of miRNA’s in pancreatic cancer; (i) diagnosis; (ii) prognosis and (iii) therapeutic intervention. Conclusion section describes the gist of review with future directions.

Discrete-trials heroin self-administration produces sensitization to the reinforcing effects of cocaine in rats

2006 ◽  
Vol 185 (2) ◽  
pp. 150-159 ◽  
Author(s):  
Sara J. Ward ◽  
Christopher Läck ◽  
Drake Morgan ◽  
David C. S. Roberts
Keyword(s):  
Self Administration ◽  
Discrete Trials ◽  
Reinforcing Effects

scholarly journals Transient-Liquid-Phase and Liquid-Film-Assisted Joining of Ceramics

2006 ◽  
Vol 45 ◽  
pp. 1568-1577 ◽  
Author(s):  
S.M. Hong ◽  
T. Akashi ◽  
J.T. McKeown ◽  
J.D. Sugar ◽  
C.C. Bartlow ◽  
...  
Keyword(s):  
Liquid Phase ◽  
Liquid Film ◽  
Critical Role ◽  
Transient Liquid Phase ◽  
Temperature Sensitive ◽  
Liquid Droplets ◽  
Metallic Films ◽  
Continuous Film ◽  
Future Directions ◽  
Transport Path

Transient-liquid-phase (TLP) joining and liquid-film-assisted joining (LFAJ) exploit thin metallic films that melt at relatively low temperatures as part of a multilayer, multimaterial interlayer to enable joining at reduced temperatures. These methods are attractive for assemblies that include temperature-sensitive components, however, unlike conventional low-temperature joining methods, they also offer the potential for service at temperatures approaching or even exceeding the original joining temperature. In successful TLP joining and LFAJ, the wetting behavior of the liquid plays a critical role. In TLP joining, the liquid ultimately disappears during joining due to interdiffusion and chemical homogenization. In contrast, in LFAJ the liquid persists at the joining temperature, provides a high-diffusivity transport path that accelerates joint formation, and ultimately undergoes a morphological transition that disrupts the initially continuous film. The resulting isolated liquid droplets solidify on cooling. Current studies of these joining methods are described, and promising future directions are indicated.

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