The Basolateral Amygdala is a Critical Structure for Environmental Cue Augmentation of EtOH-Seeking

Jessica Wilden, MD1, Sheketha Hauser, PhD1, Gerald DeehanJr, PhD1, Zheng-Ming Ding, PhD1, William Truitt, PhD1, William McBride, MD, PhD1, Zachary Rodd, PhD1

1Indianapolis, IN United States

Keywords: animal model, behavioral disorder, addiction, alcoholism, amygdala

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Abstract

     Long after cessation of drug use, addicts crave for the past substance(s).
     Environmental cues paired with previous use of a drug can enhance drug seeking; inhibitory cues associated with unavailability of a drug can reduce drug seeking. The amygdala may be a critical structure for these interactions.
     Alcohol-preferring rats were used.
     Alcohol-preferring (P) rats were exposed to three distinct odors: 1) an odor paired with the operant self-administration of EtOH (CS+) 2) an odor paired with the unavailability of EtOH (CS-) and 3) a neutral odor (CS0). Subjects were then exposed to one odor for 30 minutes in a non-drug paired environment and neuronal activity was measured through standard c-fos protocols. Microinjections of GABA agonists were then used to pharmacologically silence the bilateral basolateral amygdala (BLA) of P rats in a 2 (active drug or aCSF control injection) by 3 (CS+, CS-, or CS0) experimental design in the operant setting.
     Neuronal activity was not altered by the conditioned cues in the central or medial amygdala, but there was a 60% increase in c-fos positive neurons in the basolateral amygdala in CS+ subjects. Since BLA was only activated by the excitatory conditioned cue (CS+), activation of BLA was hypothesized to enhance EtOH-seeking. Subsequent pharmacological silencing of the BLA did not affect baseline EtOH-seeking or the inhibitory effect of the CS-, but did prevent enhancement of EtOH-seeking invoked by CS+.
     This model may not be indicative of the human condition.
     The BLA may mediate the ability of conditioned cues to enhance drug seeking.
     This region could serve as a target for intervention to reduce drug craving and relapse.


Acknowledgements

Project Roles:

J. Wilden (), S. Hauser (), G. DeehanJr (), Z. Ding (), W. Truitt (), W. McBride (), Z. Rodd ()