Figure 1.

Long-term effects of social defeat-induced persistent stress (SDPS) on social behavior and cognition. (a) Experimental schedule: individually housed animals were used (controls; n=36), or they were exposed to the prolonged social defeat stress paradigm (SDPS; n=48), after which animals were subjected to operant alcohol self-administration (SA). All animals were tested in social approach-avoidance (SAA; b), social recognition (SR; c), and object place recognition (OPR; d) before (baseline) and after defeat (week 5 or 9). After ⩾9 weeks, representatives of each group (n=16) were selected for familiarization to alcohol in the home cage and subsequent operant alcohol SA. Animals were trained in fixed (fixed ratio1( FR1)–3) and progressive ratio (PR) schedules, followed by extinction training and an alcohol-coupled cue-induced reinstatement test. The effects of guanfacine (Gua) on motivation and reinstatement of alcohol seeking were assessed in a cross-over design. (b–d) Results from the total group of animals (left) or from the selected group for subsequent alcohol SA studies (right). (b) SAA: the SDPS group exhibited a significant reduction in interaction rates in week 5 and showed no improvement in the SAA performance over time as seen in controls. (c) Control and SDPS animals displayed significant between-group differences in week 9 following defeat, and SDPS animals exhibited a reduction in interaction rate over time. (d) The SDPS group displayed a significant reduction in exploration rate (week 5) and failed to improve the OPR performance. ANOVA/t-test results are indicated (t: time effect; g: group effect; t × g: time × group interaction) *p<0.05; **p<0.01. Dashed gray lines indicate 50% preference index.