Chemogenetic inhibition of IC blocked the social affective preference for stressed PN30 conspecifics. A, Representative image of pAAV5-hSyn-hM4D(Gi)-mCherry transduction in IC (right) and corresponding rat brain atlas diagram (left). B, Map of bilateral IC pAAV5-hSyn-hM4D(Gi)-mCherry expression in experimental rats. Each subject is represented in a different color (n = 10); bold outlines represent the greatest intensity of mCherry expression and the corresponding faded overlay depicts the full extent of virus transduction. C, Map of bilateral IC sham pAAV5-hSyn-mCherry expression, n = 8. D, Diagram of SAP test procedure. E, Control experiments: Experimental rats (n = 8) without viral transduction underwent the SAP test procedure 45 min after CNO injections at 3 doses: 0, 0.3, and 3.0 mg/kg (i.p.). No dose of CNO disrupted the preference for the stressed PN30 conspecific (0 mg/kg, p = 0.0009; 0.3 mg/kg, p = 0.0036 mg/kg; 3 mg/kg, p = 0.0063). Experimental rats transduced with a sham virus (n = 9) preferred to explore the stressed PN30 conspecific under vehicle (p = 0.003) and 3 mg/kg CNO (i.p.) (p = 0.002). F, Mean (with individual replicates) time spent exploring the naive and stressed PN30 conspecifics during the 5 min trial. Vehicle-treated rats spent more time exploring the stressed PN30 conspecifics than the naive PN30 (p = 0.0001), which was abolished in trials after injections of CNO (3 mg/kg, i.p.) 45 min before testing (p = 0.517). G, Data from F and G converted to percentage preference for the stressed conspecific. The only condition in which CNO reduced the preference for the stressed PN30 conspecific was in experimental rats transduced with hM4D(Gi) (p = 0.0003). H, Representative acute, whole-cell recording of hM4D(Gi)-expressing IC neuron before and after bath application of CNO. I, After 10 min of bath application, CNO reduced the number of action potentials evoked by current injection in hM4D(Gi)-mCherry-positive neurons in the IC. (+) indicates the beginning of CNO perfusion. (ns) indicates non significant difference. *p < 0.5, **p < 0.01, ***p < 0.001.