Brief intro:
- Author: Geith Maal-Bared, Mandy Yee, Erika K. Harding, Martha Ghebreselassie, Michael Bergamini, Roxanne Choy, Ethan Kim, Stephanie Di Vito, Maryam Patel, Mohammadreza Amirzadeh, Taryn E. Grieder, James I. Nagy, Robert P. Bonin and Derek van der Kooya
- Journal: BioRxiv
- Doi: https://www.doi.org/10.1101/2020.12.18.423554
- Publication Date: 2020 Dec 21
Products/Services used in the paper
Quotation shows PackGene:These coordinates were used to deliver Cre-dependent AAVs carrying Cx36 (ssAAV9-Ef1a-DIO-Cx36) and EGFP (ssAAV9-Ef1a-EGFP-WPREs) at 5E+13 GC/mL in 0.1 mL. AAVs were obtained from Packgene.
Research Field:CNS
AAV Serotype:AAV9
Targeted organ:brain
Animal or cell line strain:Adult male Wistar rats (250 – 400 grams) and C57BL/6 mice (20 – 35 grams) were acquired from Charles River (Montreal, Canada).
Abstract
Drug dependence is characterized by a switch in motivation wherein a positively reinforcing substance becomes negatively reinforcing. Ventral tegmental area (VTA) GABA neurons form a point of divergence between two double dissociable pathways responsible for these respective motivational states. Here we show that this switch from drug-naïve to opiate-dependent and withdrawn (ODW) motivation is contingent upon the gap junction-forming protein, connexin-36 (Cx36), in VTA GABA neurons. Intra-VTA infusions of the Cx36 blocker, mefloquine, in ODW rats resulted in a reversion to a drug-naïve motivational state and a loss of opiate withdrawal aversions. Consistent with these data, conditional knockout mice lacking Cx36 in GABA neurons (GAD65-Cre;Cx36fl(CFP)/fl(CFP)) were perpetually drug-naïve and never experienced opiate withdrawal aversions. Further, viral-mediated rescue of Cx36 in VTA GABA neurons was sufficient to restore their susceptibility to ODW motivation. Our findings reveal a functional role for VTA gap junctions that has eluded prevailing circuit models of addiction.
About PackGene
PackGene Biotech is a world-leading CRO and CDMO, excelling in AAV vectors, mRNA, plasmid DNA, and lentiviral vector solutions. Our comprehensive offerings span from vector design and construction to AAV, lentivirus, and mRNA services. With a sharp focus on early-stage drug discovery, preclinical development, and cell and gene therapy trials, we deliver cost-effective, dependable, and scalable production solutions. Leveraging our groundbreaking π-alpha 293 AAV high-yield platform, we amplify AAV production by up to 10-fold, yielding up to 1e+17vg per batch to meet diverse commercial and clinical project needs. Moreover, our tailored mRNA and LNP products and services cater to every stage of drug and vaccine development, from research to GMP production, providing a seamless, end-to-end solution.
