Repeated stressful experiences affect limbic dopamine release during and following stress

Institute of Medical Pharmacology, University La Sapienza, Rome, Italy.
Brain Research (Impact Factor: 2.84). 05/1992; 577(2):194-9. DOI: 10.1016/0006-8993(92)90274-D
Source: PubMed


The effects of repeated restraint stress exposures (daily 60 min, for 6 days) on extracellular dopamine in the nucleus accumbens, during and after the stress experience, have been investigated in rats by in vivo microdialysis. On the first day, restraint increased dopamine release during the first 40 min followed by a return to basal levels (50-60 min later). As soon as restraint ceased and the rats were set free, there was another increase in dopamine release lasting 40 min. On the second and third day, restraint produced only a slight increase in dopamine release, while no significant changes were evident from the fourth to the sixth day. By contrast, from the second to the sixth day the increase in dopamine release observed once rats were freed, was unchanged in comparison to the first day. The present results show that the activation of the mesolimbic dopaminergic system induced by aversive stimuli adapts to repeated experiences differently from that produced by pleasurable events, suggesting that aversive and rewarding experiences involve different neural systems.

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Available from: Stefano Puglisi-Allegra, Aug 05, 2015
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    • "However, less is known about the effects of repeated stress on mesocorticolimbic dopamine activity. Depending on the intensity, duration, frequency, controllability , and predictability of the stressor, some have found that repeated stress causes a habituation (Imperato et al. 1992, 1993), sensitization (Jordan et al. 1994; Naef et al. 2013; Petty et al. 1997), or no change (Young 2004) in extracellular mPFC or NAcSh dopamine in response to the same stressor. VTA dopamine activity can be modulated by several neuropeptides , including CRF, one key initiator of the central and peripheral stress response. "
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    ABSTRACT: Rationale Stress activates a subset of dopamine neurons in the ventral tegmental area (VTA), increasing extracellular dopamine in the medial prefrontal cortex (mPFC) and nucleus accumbens shell (NAcSh). The stress neuropeptide corticotropin releasing factor (CRF) and its receptors (CRF-R1 and CRF-R2) are located within the VTA and directly and indirectly influence dopaminergic activity. However, it has yet to be shown in vivo whether VTA CRF receptor activation is necessary for acute and repeated stress-induced dopamine efflux. Objective With intra-VTA CRF-R1 and CRF-R2 antagonism during social defeat, we assessed whether blockade of these receptors could prevent stress-induced dopamine increases in the mPFC and NAcSh using in vivo microdialysis. Methods Rats were microinjected with a CRF-R1 or CRF-R2 antagonist into the VTA prior to social defeat stress on days 1, 4, 7, and 10. In vivo microdialysis for dopamine in the mPFC and NAcSh was performed during stress on days 1 and 10. Results During the first social defeat, extracellular dopamine was significantly elevated in both the mPFC and NAcSh, and this increase in the NAcSh was blocked by intra-VTA CRF-R2, but not CRF-R1, antagonism. During the final social defeat, the dopaminergic increase was neither sensitized nor habituated in the mPFC and NAcSh, and intra-VTA CRF-R2, but not CRF-R1, antagonism prevented the dopamine increase in both brain regions. Conclusion These findings show that CRF-R2 in the VTA is necessary for acute and repeated stress-induced dopamine efflux in the NAcSh, but is only recruited into mPFC-projecting dopamine neurons with repeated stress exposure.
    Full-text · Article · Sep 2015 · Psychopharmacology
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    • "Both leptin and insulin have been suggested to exert a regulatory function in the meso-limbic reward system, and especially insulin increased expression of dopamine transporters in the ventral tegmental area [62] [63]. As described above, the meso-limbic reward system is highly implicated in the psycho-emotional disorders in relation with the stress axis function [22] [23] [24] [25] [26] [27]. Thus, a tentative modulation , if any, in the meso-limbic reward system by increased leptin and/or insulin with increased fat depot is suggested to play a role in the mood elevation by palatable food access. "
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    ABSTRACT: This study examined the effects of highly palatable food during adolescence on the psycho-emotional and neural disturbances caused by early life stress experience in female rats. Female Sprague-Dawley pups were separated from dam for 3 h daily during the first two weeks of birth (MS) or left undisturbed (NH). Half of MS females received free access to chocolate cookies in addition to ad libitum chow from postnatal day 28. Pups were subjected to the behavioral tests during young adulthood. The plasma corticosterone response to acute stress, ΔFosB and brain-derived neurotrophic factor (BDNF) levels in the brain regions were analyzed. Total caloric intake and body weight gain during the whole experimental period did not differ among the experimental groups. Cookie access during adolescence and youth improved anxiety-/depression-like behaviors by MS experience. ΔFosB expression was decreased, but BDNF was increased in the nucleus accumbens of MS females, and ΔFosB expression was normalized and BDNF was further increased following cookie access. Corticosterone response to acute stress was blunted by MS experience and cookie access did not improve it. Results suggest that cookie access during adolescence improves the psycho-emotional disturbances of MS females, and ΔFosB and/or BDNF expression in the nucleus accumbens may play a role in its underlying neural mechanisms.
    Full-text · Article · Sep 2015 · International journal of biological sciences
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    • "It has been reported that reduced dopaminergic function within the NAc may cause depression-like behaviors in rodents [44], and the striatal dopaminergic activity was suggested to be associated with the severity of anhedonia in depressed patients [45]. The NAc is activated in response to behavioral stress paradigm [46,47], suggesting its implication in the stress-responsive HPA axis regulation. Rats that experienced our MS protocol showed not only HPA axis dysfunction but also reduced dopaminergic activity in the NAc [48]. "
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    ABSTRACT: Background This study was conducted to examine the effects of ad libitum consumption of highly palatable food (HPF) during adolescence on the adverse behavioral outcome of neonatal maternal separation. Methods Male Sprague-Dawley pups were separated from dam for 3 hours daily during the first 2 weeks of birth (maternal separation, MS) or left undisturbed (nonhandled, NH). Half of MS pups received free access to chocolate cookies in addition to ad libitum chow from postnatal day 28 (MS+HPF). Pups were subjected to behavioral tests during young adulthood. The plasma corticosterone response to stress challenge was analyzed by radioimmunoassay. Results Daily caloric intake and body weight gain did not differ among the experimental groups. Ambulatory activities were decreased defecation activity and rostral grooming were increased in MS controls (fed with chow only) compared with NH rats. MS controls spent less time in open arms, and more time in closed arms during the elevated plus maze test, than NH rats. Immobility duration during the forced swim test was increased in MS controls compared with NH rats. Cookie access normalized the behavioral scores of ambulatory and defecation activities and grooming, but not the scores during the elevated plus maze and swim tests in MS rats. Stress-induced corticosterone increase was blunted in MS rats fed with chow only, and cookie access normalized it. Conclusion Prolonged access to HPF during adolescence and youth partly improves anxiety-related, but not depressive, symptoms in rats that experienced neonatal maternal separation, possibly in relation with improved function of the hypothalamic-pituitary-adrenal (HPA) axis.
    Full-text · Article · Jun 2014
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