Accumbal Dopamine Responses Are Distinct between Female Rats with Active and Passive Coping Strategies

Abstract

There is a gap in existing knowledge of stress-triggered neurochemical and behavioral adaptations in females. This study was designed to explore the short-term consequences of a single social defeat (SD) on accumbal dopamine (DA) dynamics and related behaviors in female Wistar rats. During the SD procedure, rats demonstrated different stress-handling strategies, which were defined as active and passive coping. The "active" subjects expressed a significantly higher level of activity directed toward handling stress experience, while the "passive" ones showed an escalated freezing pattern. Remarkably, these opposite behavioral manifestations were negatively correlated. Twenty-four hours following the SD exposure, decreased immobility latency in the Porsolt test and cognitive augmentation in the new object recognition evaluation were evident, along with an increase in electrically evoked mesolimbic DA release in passive coping rats. Rats exhibiting an active pattern of responses showed insignificant changes in immobility and cognitive performance as well as in evoked mesolimbic DA response. Furthermore, the dynamics of the decline and recovery of DA efflux under the depletion protocol were significantly altered in the passive but not active female rats. Taken together, these data suggest that female rats with a passive coping strategy are more susceptible to developing behavioral and neurochemical alterations within 24 h after stress exposure. This observation may represent both maladaptive and protective responses of an organism on a short timescale.

Keywords: dopamine release; female rats; nucleus accumbens; social defeat; stress coping.

Figure 1

Schematic illustration of the experimental design: (A) Two groups of female Wistar rats were exposed to two different behavioral paradigms. In the first one, an intruder rat was reintroduced to its non-aggressive cagemate. These rats were housed together for at least 4 weeks. They interacted without any confrontation. In the latter paradigm, a subject was placed in the cage with a Tph2-KO resident. The intruder and aggressive resident were introduced to each other for the first time. All rats underwent either behavioral testing or in vivo fast-scan cyclic voltammetry (FSCV) measurements 24 h after SD. (B) Schematic illustration of a time course of the single SD procedure.

Figure 2

Upper panel: Behavioral patterns displayed by control rats during non-aggressive social interaction ((A), n = 20) and by intruder rats with passive ((B), n = 16) or active ((C), n =18) coping with the aggressiveness of Tph2-KO residents during the direct contact phase of single SD episode. Lower panel: Display of passive ((D), freezing) or active ((E), exploration + attacks + defense + running + grooming + digging) behavior by control and active or passive coping with SD stress rats. All data are mean ± SEM, expressed as a ratio (%) of total evaluation time, 10 min; levels of statistical significance: **—p < 0.01; ***—p < 0.001; ****—p < 0.0001. (F) Scatter plot of negative correlation between exploratory activity and freezing behavior of intruder rats under stress during the direct contact phase of SD.

Figure 3

The behavior of rats displayed 24 h following non-aggressive social interactions (control) and SD episodes. Rats were tested in the standard battery of behavioral assessments, including (A) sucrose intake test, (B) novel object recognition, (C) Porsolt forced swim (time and latency of immobility) and (D,E) elevated plus maze tests. Color-coded columns were designated for the following experimental groups of rats: active coping (blue, n = 7), passive coping (green, n = 8) and control (grey, n = 15). All data expressed as mean ± SEM, * p ≤ 0.05; # p = 0.06.

Figure 4

Alterations of electrically evoked DA response in rats with different coping observed 24 h after the single SD stress: (A) representative DA signals in response to the stimulation (60 Hz, 60 pulses, current 330 µA); (B) electrically evoked DA was released in a frequency-dependent manner in all tested groups, while the response was significantly higher in passively coping rats; (C) SD stress resulted in changes in DA efflux after the depletion (3 × 10 s, 60 Hz, 600 pulses, 330 µA) and during recovery processes; (D) changes (%) in DA depletion and recovery levels observed within 15 min following the VTA stimulation. Data are presented as mean ± SEM, repeated measures two-way ANOVA and Kruskal–Wallis test; *—p < 0.05; **—p < 0.01; ***—p ≤ 0.001; ****—p < 0.0001.