Authors:

Nistha Agarwal

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About Paper:

Ethanol (EtOH) produces rewarding and aversive effects that influence drinking behavior, yet mechanisms underlying its aversive properties are not well defined. The anterior insular cortex (AIC) processes interoceptive signals and its disruption impairs aversive responding, suggesting a role in encoding the negative internal effects of EtOH. The AIC also sends direct input to the rostromedial tegmental nucleus (RMTg), a GABAergic nucleus that encodes aversive stimuli, suggesting a pathway mediating EtOH's aversive properties. To examine this, we used a chemogenetic approach to temporarily inactivate the AIC during conditioned taste aversion (CTA) — a preclinical paradigm used to measure the aversive properties of drugs. Male and female Long-Evans rats received bilateral injections of a viral vector expressing either GFP or Gi-coupled DREADD into the AIC. Following recovery, rats underwent CTA training in which a 0.1% saccharin solution was paired with an injection of saline, EtOH (1.5 g/kg), or LiC! (31.75 mg/kg) across three conditioning sessions. On test day, rats were given saccharin without a drug injection. The effect of AIC inactivation on CTA was assessed in separate groups that received clozapine-N-oxide (CNO; 1 mg/kg, i.p.) 30 minutes before saccharin. Inactivating the AIC on test day did not affect CTA expression for any drug (p>0.05). However, DREADD-expressing rats in the EtOH group that received CNO during conditioning trials drank significantly more saccharin compared to GFP controls (*p<0.03). AIC inactivation during conditioning had no effect on LiCl-induced CTA (p>0.05). These findings suggest that AIC activity is required for learning to associate EtOH's aversive interoceptive effects with the saccharin cue but is not necessary for the expression of this association when AIC activity is undisturbed during conditioning. Ongoing experiments explore whether selective inactivation of RMTg-projecting AIC neurons produces a similar effect. These data will provide evidence for a circuit-level mechanism integrating interoceptive processing with aversive signaling. GOGH OHO HES SEH SEC OH OCC OHO SOSH SOOO HST OHSS OC OCHS SCOHOO POCO OOOOEO @DDHDHDFIDDIDIDHHHDHDFIFDDDDHDSDIDHDIDHVIDIDDIDD

Source:

University of Illinois Chicago

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Co-authors:

Nistha Agarwal