The Effect of Stressor Controllability on Social Hedonic Preference in Laboratory Rats
Introduction. Major Depressive Disorder (MDD) is a devastating mood disorder characterized by social anhedonic deficits. Stress and MDD are inextricably linked, however, not all stressors have the same impact on depressive symptomology. Uncontrollable stress causes anhedonic deficits that are mitigated when the same stressor is controllable, and this has been shown to be regulated by serotonin. The current thesis investigates whether stressor controllability affects social reward processing in laboratory rodents as well as the associated neurobiological mechanisms regulating this effect. Methods. In order to investigate this, a procedure was developed that assessed both social unconditioned and conditioned reward reactivity in male Sprague-Dawley rats. Rats were then exposed to escapable or yoked inescapable foot shocks and were tested in this social preference procedure. The selective serotonin reuptake inhibitor escitalopram (ESC), a putative antidepressant drug, was administered after shock exposure to determine whether stressor controllability and social hedonic reactivity were regulated by serotonergic mechanisms. In vivo microdialysis was used to determine whether extracellular serotonin in the dorsal hippocampus was affected by stressor controllability and ESC treatment in a conditioned social environment. Finally, the effect of stressor controllability on social hedonic preference was assessed in female Sprague-Dawley rats, because MDD is more prevalent in women compared to men. Results. In male Sprague-Dawley rats, it was found that exposure to inescapable stress caused deficits in social conditioned but not unconditioned preference, and this was mitigated when the same stressor was controllable. Treatment with ESC attenuated the effects of inescapable stress on social conditioned preference. Furthermore, ESC treatment was associated with elevated extracellular serotonin levels in the dorsal hippocampus. Female rats showed a reduced social conditioned preference sensitivity compared to males, and despite this inescapable stress reduced social conditioned preference after exposure to inescapable, but not escapable shocks. Conclusion. The effect of stressor controllability had a significant impact on social conditioned preference in laboratory rats, and this was regulated by serotonergic mechanisms. This suggests that the ability to control aversive stimuli significantly attenuates the deleterious consequences of stress on social reward processing, and this has important implications for preventing this cardinal feature of MDD.