Dopamine (DA) neurons respond to unexpected food delivery and are inhibited during the omission of expected reward. DA receptor blockade mimics some, but not all, aspects of non-reward (extinction) conditions. It was therefore of interest to ask whether DA receptor blockade produces extinction-like increases in behavioral variability in addition to its well-known operant response-suppressing effects. In the current experiment, rats were trained drug-free on an operant task in which they pressed on a keyboard. Two of the keys led to food on a continuous reinforcement schedule. Both response rates and behavioral variability were measured. Test day administration of D(1) and D(2) antagonists SCH23390 and raclopride, like extinction, suppressed responding but, unlike extinction, did not lead to an increase in variability.
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http://dx.doi.org/10.1037/0735-7044.120.2.488 | DOI Listing |
Sci Rep
January 2025
Department of Physiology, Zunyi Medical University, Campus No.1 Road, Xinpu New District, Zunyi, 563006, Guizhou, China.
In the vascular system, angiotensin II (Ang II) mediated vasoconstriction by inducing the production of 20-hydroxyeicosatetraenoic acid (20-HETE). However, the role of 20-HETE in Ang II-induced cardiac dysfunction had yet to be fully elucidated. This study investigated the effects of Ang II on CYP4A expression and 20-HETE production in H9c2 cells using RT-qPCR, Western blot, and ELISA.
View Article and Find Full Text PDFCell Mol Gastroenterol Hepatol
January 2025
Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ, USA. Electronic address:
Background & Aims: Erythropoietic protoporphyria (EPP) is caused by mutations in ferrochelatase which inserts iron into protoporphyrin-IX (PP-IX) to generate heme. EPP is characterized by PP-IX accumulation, skin photosensitivity, cholestasis, and end-stage liver disease. Despite available drugs that address photosensitivity, treatment of EPP-related liver disease remains an unmet need.
View Article and Find Full Text PDFAdv Exp Med Biol
January 2025
Lester & Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
HER2-positive (+) breast cancer is an aggressive disease with poor prognosis, a narrative that changed drastically with the advent and approval of trastuzumab, the first humanized monoclonal antibody targeting HER2. In addition to another monoclonal antibody, more classes of HER2-targeted agents, including tyrosine kinase inhibitors, and antibody-drug conjugates were developed in the years that followed. While these potent therapies have substantially improved the outcome of patients with HER2+ breast cancer, resistance has prevailed as a clinical challenge ever since the arrival of targeted agents.
View Article and Find Full Text PDFAdv Exp Med Biol
January 2025
Division of Cancer Sciences, University of Manchester, Manchester, UK.
There has been over 130 years of research into the treatment of breast cancer using approaches that target oestrogen receptor signalling. Here, we summarise the development of the key pillars of such endocrine therapy, namely, oestrogen deprivation, achieved through ovarian suppression and/or aromatase inhibition, and oestrogen receptor blockade, through selective oestrogen receptor modulators, downregulators and novel compounds entering early phase development. The translation of these compounds from advanced to early breast cancer settings is discussed with a focus on the placebo-controlled breast cancer prevention studies to most accurately describe the side effect profiles of the main approaches.
View Article and Find Full Text PDFClin Adv Hematol Oncol
December 2024
Department of Pediatrics, New York Medical College, Valhalla, New York.
Childhood and adolescent classic Hodgkin Lymphoma (cHL) has long been a model for how we balance improved outcomes with increased toxicities in pediatric cancer. The recognition that unacceptable short- and long-term toxicities come with increasing intensity of treatment has led to a decades-long attempt to better understand the patient-specific factors that dictate responses and outcomes. Targeted immunotherapy has emerged as a promising adjunct to cancer treatment; it has been shown to improve outcomes for poorly responding patients, to salvage relapsed disease, and more recently, to replace more toxic therapy modalities such as chemotherapy and radiation while maintaining excellent outcomes.
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