Fig. 2A (top). Sensitization of alcohol withdrawal-induced anxiety (reduced social interaction) with repeated stresses. Male rats were exposed to either continuous control diet or to stress applied at 6 and 11 days while on CD followed by a single 5-day cycle of 4.5% ethanol liquid diet (2STR-ETOH-Cy1). Social interaction testing commenced between 5 and 6-h after the ethanol exposure ended.
2STR-ETOH-Cy1 = two stresses + ethanol + withdrawal. Control Diet-3STR = stressed at 6, 11, and 16 days. ETOH-Cont-2STR = stress at 6 and 11 days during continuous (Cont) ethanol diet + withdrawal. **p < 0.01 compared to CD or CD-3STR. Adapted from Breese et al., 2004.
Fig. 2B (middle). Effect of a CRF-1R antagonist administered prior to testing for stress-induced reductions in social interaction behavior at three days into abstinence from repeated alcohol withdrawals. The CRF-1R antagonist CP-154,526 (10 mg/kg) was administered 30 min prior to restraining of rats for 45 min on day 3 after the last of three withdrawals. Vehicle (Veh) was given to rats exposed to ethanol (alcohol) diet and stress (ED Stress Veh). CP-154,526 significantly blocked the deficit induced by stress in repeatedly withdrawn rats (*p < 0.01 compared to Control Diet group with no stress). Adapted from Breese et al., 2005.
Fig. 2C (bottom). Effect of a CRF-1R antagonist administered during repeated withdrawals on subsequent behavioral responses to stress three days into abstinence from repeated alcohol withdrawals. The CRF1-receptor antagonist, CP-154,526 (10 mg/kg) was administered during the first two withdrawal periods, but not the final withdrawal, of the multiple withdrawal protocol. Vehicle was given to the group that received alcohol diet and stress (ED Stress Veh). CP-154,526 significantly prevented the reduction in social interaction induced by stress applied three days following the repeated withdrawals. *p < 0.01 compared to ED No Stress, Control Diet Stress, and Control Diet No Stress groups and CP-154,526 group. Adapted from Breese et al., 2005.