The central nucleus of the amygdala (CeA) has a critical role in regulating ethanol consumption and the response to ethanol withdrawal. We previously demonstrated that rat CeA GABAergic transmission is enhanced by acute and chronic ethanol treatment. Here, we used quantitative RT-PCR (qRT-PCR) to detect Ghsr mRNA in the CeA and performed electrophysiological recordings to measure ghrelin effects on GABA transmission in this brain region. Furthermore, we examined whether acute or chronic ethanol treatment would alter these electrophysiological
effects. Our qRT-PCR studies show the presence of Ghsr mRNA in the CeA. In naive animals, superfusion of ghrelin increased the amplitude of evoked inhibitory postsynaptic potentials (IPSPs) and the frequency of miniature inhibitory postsynaptic currents (mIPSCs). Coapplication of ethanol further increased GSK621 the ghrelin-induced enhancement of IPSP amplitude, but to a lesser extent than ethanol alone. When applied alone, ethanol significantly increased IPSP amplitude, but this effect was attenuated by the application of ghrelin. In neurons
from chronic ethanol-treated (CET) animals, the magnitude of ghrelin-induced increases in IPSP amplitude Blasticidin S ic50 was not significantly different from that in naive animals, but the ethanol-induced increase in amplitude was abolished. Superfusion of the GHS-RIA antagonists D-Lys3-GHRP-6 and JMV 3002 decreased evoked IPSP and mIPSC frequency, revealing tonic ghrelin activity in the CeA. D-Lys3-GHRP-6 and JMV 3002 also blocked ghrelin-induced increases in GABAergic responses. Furthermore, D-Lys3-GHRP-6 did not affect ethanol-induced increases EPZ015666 in IPSP amplitude. These studies implicate a potential role for the ghrelin system in regulating GABAergic transmission and a complex interaction with ethanol at CeA GABAergic synapses. Neuropsychopharmacology (2013) 38, 364-375; doi:10.1038/npp.2012.190; published online 12 September 2012″
of antibody-based cancer therapeutics has led to the concomitant rise in the development of companion diagnostics for these therapies, particularly nuclear imaging agents. A number of radioisotopes have been employed for antibody-based PET and SPECT imaging, notably Cu-64, I-124, In-111, and Tc-99m: in recent years. however, the field has increasingly focused on Zr-89, a radiometal with near ideal physical and chemical properties for immunoPET imaging. In the review at hand, we seek to provide a comprehensive portrait of the current state of Zr-89 radiochemical and imaging research, including work into the production and purification of the isotope, the synthesis of new chelators, the development of new bioconjugation strategies, the creation of novel Zr-89-based agents for preclinical imaging studies, and the translation of Zr-89-labeled radiopharmaceuticals to the clinic.