Basolateral amygdala inhibition reduces avoidance in conditioned taste aversion—Transient chemogenetic silencing shifts behavior toward sustained licking

Abstract

The basolateral amygdala (BLA) plays a critical role in aversive learning and decision‑making, yet its specific contribution to the expression of conditioned taste aversion (CTA) remains incompletely understood. Here, we examined how transient chemogenetic inhibition of the BLA influences licking microstructure and approach–avoidance behavior toward a conditioned saccharin solution. Male C57BL/6 mice received bilateral BLA injections of AAV8‑hSyn‑hM4Di‑mCherry (experimental) or AAV8‑hSyn‑mCherry (control). CTA was induced by pairing saccharin (CS) with LiCl (US). Following CTA acquisition, animals were tested drug‑free (Test 1), after CNO or saline administration (Test 2), and drug‑free on the subsequent day (Test 3). In Test 2, CNO‑treated hM4Di‑expressing mice showed increased total licking, larger mean burst sizes, and a greater frequency of large bursts (>200 licks), accompanied by longer Entry‑Lick durations and reduced Entry‑Stop durations. Event‑based analyses confirmed fewer prolonged pauses and more sustained licking bouts in this group. These effects were absent in control groups and did not persist into Test 3, indicating a short‑lived influence on behavioral expression without erasure of the aversive memory. Together with previous manganese‑enhanced MRI evidence of BLA projections to the central amygdala, nucleus accumbens, and bed nucleus of the stria terminalis engaged during CTA expression, these results suggest that BLA activity modulates moment‑to‑moment avoidance through its downstream circuits. The findings provide new insight into the amygdala’s role in regulating complex ingestive behaviors and highlight potential neural targets for modifying maladaptive avoidance.