Modeling hypohedonia following repeated social defeat: Individual vulnerability and dopaminergic involvement

Abstract

Social defeat in rodents putatively can model hypohedonia. The present studies examined models for assessing hypohedonia-like behavior and tested the hypotheses that 1) individual differences in baseline reward sensitivity predict vulnerability, and 2) defeat elicits changes in pharmacological measures of striatal dopaminergic function. Male Wistar rats (n=142) received repeated defeat (3 “triad” blocks of 3 defeats) or control handling. To determine whether defeat influenced consumption of SuperSac (glucose-saccharin) over an isocaloric, less preferred, glucose solution, a 2-choice paradigm was used. To determine repeated defeat effects on the reinforcing efficacy of SuperSac, a progressive-ratio schedule of reinforcement was used. Amphetamine-induced locomotor activity (0.08 mg/kg, s.c.) was determined as a measure sensitive to striatal dopaminergic function. Defeat reduced SuperSac consumption during the first two triads—an effect seen in the third triad only in defeated rats with High vs. Low baseline SuperSac intake. The characteristic escalation in PR breakpoint for SuperSac normally seen in controls was absent in defeated rats, leading to a significant difference by the third triad. Defeat-induced blunting of the escalation in PR performance was greater in rats with High antecedent PR breakpoints and persisted 2.5 weeks post-defeat. Repeated defeat also blunted amphetamine-induced locomotion 13 days post-defeat. Thus, hypohedonic-like effects of social defeat were detected and accompanied by persistently attenuated striatal dopamine function. Early effects were seen for consumption of differentially-palatable solutions, and persistent effects were seen for the “breakpoint” motivational measure. The results implicate initial reward sensitivity as a risk factor for stress-induced hypohedonia.

Making Sense of Rodent Models of Anhedonia

“…Thus, a decrease in breaking point may be regarded as a core symptom in animal models of anhedonia, although this decrease is not reliably observed in all the models. Reductions in breakpoints for sucrose have been reported in a genetic animal model of depression, the congenital learned helpless rat ( Vollmayr et al, 2004 ), in a chronic unavoidable stress protocol in rats ( Marchese et al, 2013 ; Scheggi et al, 2016 ), and in rats and mice exposed to chronic social defeat ( Bergamini et al, 2016 ; Spierling et al, 2017 ). This index of reduced motivation for a natural reward can be restored to control values by treatments endowed with antidepressant and/or promotivational activity, for example, lithium, clozapine, aripiprazole, and lamotrigine ( Marchese et al, 2013 ; Scheggi et al, 2015 , 2017b ; Scheggi, Pelliccia, De Montis and Gambarana, unpublished data).…”

Ethanol Reinforcement Elicits Novel Response Inhibition Behavior in a Rat Model of Ethanol Dependence

“…The progressive-ratio schedule that was utilized herein was more challenging than the one that was used by Vendruscolo et al [ 76 ], which may explain the absence of a higher breakpoint or number of reinforcers that were earned in the ETHANOL-CIE group. The more stringent schedule was adopted to compensate for the assumed increase in the palatability of the ethanol reinforcer that was caused by the addition of sucrose and saccharin [ 38 , 39 ]. Stress-mediated alterations of hedonic states in CIE rats may have contributed to the early plateau of progressive-ratio responding in CIE rats [ 39 , 48 , 80 , 81 , 82 , 83 ] and to the greater efficiency of DRL responding [ 84 ].…”

“…The more stringent schedule was adopted to compensate for the assumed increase in the palatability of the ethanol reinforcer that was caused by the addition of sucrose and saccharin [ 38 , 39 ]. Stress-mediated alterations of hedonic states in CIE rats may have contributed to the early plateau of progressive-ratio responding in CIE rats [ 39 , 48 , 80 , 81 , 82 , 83 ] and to the greater efficiency of DRL responding [ 84 ]. Finally, the association between lower impulsivity with higher progressive-ratio responding was quite unique because greater motivation is often associated with greater impulsivity.…”

“…A single-speed single-syringe pump (PHM-100, Med Associates, St. Albans, VT, USA) was available in each operant chamber to deliver the ethanol solution (10% w / v ethanol in an aqueous medium of 1.5% w / v sucrose and 1.25% w / v saccharin sodium) from a plastic syringe to the sipper cup. This sweetened ethanol solution was similar to the previously described Supersac [ 38 , 39 ] and was selected to elicit high response rates that are not normally achievable using simply a 10% ethanol solution [ 25 , 26 ].…”

Corticotropin-Releasing Factor Receptors in the Locus Coeruleus Modulate the Enhancement of Active Coping Behaviors Induced by Chronic Predator Odor Inoculation in Mice

“…As the core neurohormone to initiate the stress response, corticotropin-releasing factor (CRF) has extensive neural connections with monoamine transmitters system (Henckens et al, 2016;Spierling et al, 2017), which is the most important stress system in brain, and plays an important role in stress response and coping strategies, but how are these systems involved in the process of stress inoculation is not clear. Many investigations indicate that the dorsal raphe nuclei (DRN) 5-HT system is compelling as a target of CRF given the established role of this system in stress coping (Lesch, 2001;Schindler et al, 2012).…”