The Basolateral Amygdala is a Critical Structure for Environmental Cue Augmentation of EtOH-SeekingKeywords: amygdala, alcoholism, addiction, behavioral disorder, animal modelInteractive Manuscript
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What is the background behind your study?
Long after cessation of drug use, addicts crave for the past substance(s).
What is the purpose of your study?
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.
Describe your patient group.
Alcohol-preferring rats were used.
Describe what you did.
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.
Describe your main findings.
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+.
Describe the main limitation of this study.
This model may not be indicative of the human condition.
Describe your main conclusion.
The BLA may mediate the ability of conditioned cues to enhance drug seeking.
Describe the importance of your findings and how they can be used by others.
This region could serve as a target for intervention to reduce drug craving and relapse.
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.
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