Frustrative nonreward: Chemogenetic inactivation of the central amygdala abolishes the effect of reward downshift without affecting alcohol intake
Section snippets
Experiment 1
The DREADDs procedure involves infusing an engineered G protein-coupled muscarinic receptor modified to respond only to the synthetic compound clozapine N-oxide (CNO) (Urban & Roth, 2015). The infusion is done before training starts and, once the receptor is genetically expressed within the target area, a systemic administration of CNO activates the receptor. CNO activates the DREADD producing either neural excitation or inhibition, depending on the type of engineered receptor infused. CNO can
Subjects
Fifty-two male Wistar rats, experimentally naïve and 90 days old at the start of the experiment served as subjects. The mean (SEM) ad lib weight of the 30 animals selected for analysis (see below) was 515.6 g (13.3 g). The maintenance conditions were the same described for Experiment 1.
Surgery
All animals were subjected to the surgical procedure. In preparation for surgery, animals were food deprived to 90% of their average free-food weights and anesthetized with inhalation isoflurane (5% for
Discussion
Chemogenetic inactivation of the CeA on sessions involving reward downshift eliminated the cSNC effect. This effect of CeA inactivation is in line with the results of previous experiments using permanent lesions (Becker et al., 1984) and reversible lidocaine inactivation (Kawasaki et al., 2015). In these previous experiments, the lesion and inactivation were not as restricted to the CeA as in the present case. This confirms that neurons located in this output nucleus from the amygdala are
Acknowledgments
The National Institute on Drug Abuse (NIDA) provided the clozapine N-oxide (CNO) used in this study. This research was partially funded by TCU/SERC grants received by S. Guarino (#17005) and Z. Wade (# 180329). The authors thank I. Muzzio and K. C. Leong for their help with the understanding of the DREADD technique, Y. Liu for providing access to the fluorescence microscope for processing images, C. Torres for comments on an earlier version of this article, and Z. Wade and Q. Nguyen for their
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