Control over a stressor involves the posterior dorsal striatum and the act/outcome circuit

Abstract

Controllable/escapable tailshocks (ESs) do not produce the behavioral and neurochemical outcomes produced by equal yoked uncontrollable/inescapable tailshocks (ISs). The prelimbic cortex is known to play a key role in mediating the protective effects of control. The concepts of act/outcome learning and control seem similar, and act/outcome learning is mediated by a circuit involving the prelimbic cortex and posterior dorsomedial striatum (DMS). Thus, we tested the involvement of the DMS in the protective effect of ES, in rats. First, we examined Fos immunoreactivity in both the DMS and dorsolateral striatum (DLS) after ES and yoked IS. We then investigated the effect of blocking DMS or DLS N-methyl-d-aspartate receptors with the specific antagonist D-(-)-2-amino-5-phosphopentanoic acid (D-AP5) on the release of dorsal raphe nucleus serotonin (5-HT) during ES, as well as on the level of anxiety produced by the ES experience 24 h later. ES, but not yoked IS, produced a large increase of Fos activity in the DMS. Consistent with the Fos data, D-AP5 in the DMS, but not in the DLS, prevented the inhibition of dorsal raphe nucleus 5-HT release normally produced by ES. Furthermore, D-AP5 administered into the DMS before ES, but not into the DLS, increased anxiety 24 h later, leading to levels similar to those produced by IS. These results suggest that, as with appetitive act/outcome contingency learning, the protective effects of behavioral control over a stressor require the DMS.

Keywords: 5-HT; action control; raphe nuclei; rat; stress; striatum.

Fig. 1

Top – Illustration of regions of interest for Fos quantification in the posterior DMS or posterior DLS. Adapted from Paxinos & Watson (1998) with permission from Elsevier. Middle – Example digital photomicrograph depicting Fos immunoreactivity (black ovoid particles) in the DMS and DLS, which are outlined with dashed lines. Bottom – Mean (± SEM) number of Fos-immunoreactive cells per rat in the DMS and DLS. *Exposure to ES led to a selective increase in Fos immunoreactivity within the DMS compared with controls and both ES and IS increased Fos immunoreactivity within the DLS (P-values < 0.05).

Fig. 2

Microinjection and dialysis cannula placements. (A) Gray areas represent the sector where the injector tips were located. (B) Gray bars represent the placement of microdialysis probes. Numerals indicate distance from Bregma (in mm). Illustrations adapted from Paxinos & Watson (1998) with permission from Elsevier.

Fig. 3

Effects of NMDA receptor blockade in the dorsal striatum. (A) Wheel-turn escape latency during exposure to controllable tailshock (ES) in rats that had received DMS or DLS D-AP5 or vehicle prior to stress. Mean (± SEM) time to reach the escape criterion per five-trial block. (B) Mean (± SEM) time spent in exploration during a 3-min juvenile social encounter. At 24 h previously, rats received DMS or DLS microinjections of D-AP5 or vehicle followed by ES or IS or remained as HCC rats. *IS significantly reduced social exploration compared with ES and HCC rat vehicle groups (P-values < 0.05). ^#ES rats treated with D-AP5 in the DMS differed from HCC rat–vehicle and ES–vehicle groups (P-values < 0.05). (C) 5-HT as a percentage of baseline in the caudal DRN (mean ± SEM) before, during and after 100 escapable tail-shocks (depicted in black bar). The arrow indicates the time of injection of D-AP5 in either the DMS or DLS. For comparison to previous data examining 5-HT after controllable or uncontrollable stress without microinjections, a dotted line is added to represent 5-HT levels in response to a similar ES exposure and a dashed line in response to IS, both taken from Amat et al. (2005). D-AP5 in the DMS led to significant increase in 5-HT (P-values < 0.05).