Browsing by Subject "Adrenalectomy"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Publication
    Open Access
    Different contribution of glucocorticoids in the basolateral amygdala to the formation and expression of opiate withdrawal-associated memories
    (Elsevier, 2016-10-08) Ferenczi, Szilamer; Kovács, Krisztina J.; Núñez Parra, Cristina; García Pérez, Daniel; Laorden Carrasco, María Luisa; Milanés Maquilón, María Victoria; Farmacología; Facultades de la UMU::Facultad de Medicina
    Drug-withdrawal aversive memories generate a motivational state leading to compulsive drug taking, with plasticity changes in the basolateral amygdala (BLA) being essential in aversive motivational learning. The conditioned-place aversion (CPA) paradigm allows for measuring the negative affective component of drug withdrawal. First, CPA triggers association between negative affective consequences of withdrawal with context (memory consolidation). Afterwards, when the animals are re-exposed to the paired environment, they avoid it due to the association between the context and aversive memories (memory retrieval). We examined the influence of glucocorticoids (GCs) for a morphine-withdrawal CPA paradigm, along with plasticity changes in the BLA, in sham-operated and adrenalectomized (ADX) animals. We demonstrated that sham + morphine animals robustly displayed CPA, whereas ADX-dependent animals lacked the affective-like signs of opiate withdrawal but displayed increased somatic signs of withdrawal. Glucocorticoid receptor (GR) actions promote memory consolidation but highly depend on increases in GC levels. Interestingly, we observed that GCs were only increased in sham-dependent rodents during aversive-withdrawal memory consolidation, and that GR expression correlated with phosphorylated cAMP response element binding (pCREB) protein, early growth response 1 (Egr-1) and activity-regulated cytoskeletal-associated (Arc) mRNA induction in this experimental group. In contrast, ADX-animals displayed reduced (pCREB). GCs are also known to impair memory retrieval. Accordingly, we showed that GCs levels remained at basal levels in all experimental groups following memory retrieval, and consequently GRs no longer acted as transcriptional regulators. Importantly, memory retrieval elicited increased pCREB levels in sham + morphine animals (not in ADX + morphine group), which were directly correlated with enhanced Arc mRNA/protein expression mainly in glutamatergic neurons. In conclusion, context-withdrawal associations are accompanied plasticity changes in the BLA, which are, in part, regulated by GR signaling. Moreover, dysregulation of CREB signaling, in part through Arc expression, may enhance reconsolidation, resulting in the maintenance of excessive aversive states. These findings might have important implications for drug-seeking behavior.
  • Thumbnail Image
    Publication
    Open Access
    Distinct regulation pattern of Egr-1, BDNF and Arc during morphine-withdrawal conditioned place aversion paradigm: role of glucocorticoids
    (Elsevier, 2018-12-18) García Pérez, Daniel; Ferenczi, Szilamer; Kovács, Krisztina J.; Milanés Maquilón, María Victoria; Farmacología; Facultades de la UMU::Facultad de Medicina
    Negative affective aspects of opiate abstinence contribute to the persistence of substance abuse. Importantly, interconnected brain areas involved in aversive motivational processes, such as the ventral tegmental area (VTA) and medial prefrontal cortex (mPFC), become activated when animals are confined to withdrawal-paired environments. In the present study, place aversion was elicited in sham and adrenalectomized (ADX) animals by conditioned naloxone-precipitated drug withdrawal following exposure to chronic morphine. qPCR was employed to detect the expression of brain derived neurotrophic factor (Bdnf) and the immediate early genes (IEG) early growth response 1 (Egr-1) and activity-regulated cytoskeletal-associated protein (Arc) mRNAs in the VTA and mPFC at different time points of the conditioned place aversion (CPA) paradigm: after the conditioning phase and after the test phase. Sham + morphine rats exhibited robust CPA, which was impaired in ADX + morphine animals. Egr-1 and Arc were induced in the VTA and mPFC after morphine-withdrawal conditioning phase. Furthermore, Bdnf expression was enhanced in the VTA during the test phase. Bdnf induction seemed to be glucocorticoid-dependent, given that was correlated with HPA axis function and was not observed in morphine-dependent ADX animals. In addition, BDNF regulation and function was opposite in the VTA and mPFC during aversive-withdrawal memory retrieval. Our results suggest that IEGs and BDNF in these brain regions may play key roles in mediating the negative motivational component of opiate withdrawal.
  • Thumbnail Image
    Publication
    Open Access
    Glucocorticoid homeostasis in the dentate gyrus is essential for opiate withdrawal-associated memories
    (Springer, 2016-10-11) García Pérez, Daniel; Ferenczi, Szilamer; Kovács, Krisztina J.; Núñez Parra, Cristina; Laorden Carrasco, María Luisa; Milanés Maquilón, María Victoria; Farmacología; Facultad de Medicina
    Drug-withdrawal-associated aversive memories might trigger relapse to drug-seeking behavior. However, changes in structural and synaptic plasticity, as well as epigenetic mechanisms, which may be critical for long-term aversive memory, have yet to be elucidated. We used male Wistar rats and performed conditioned-place aversion (CPA) paradigm to uncover the role of glucocorticoids (GCs) on plasticity-related processes that occur within the dentate gyrus (DG) during opiate-withdrawal conditioning (memory formation-consolidation) and after reactivation by re-exposure to the conditioned environment (memory retrieval). Rats subjected to conditioned morphine-withdrawal robustly expressed CPA, while adrenalectomy impaired naloxone-induced CPA. Importantly, while activity-regulated cytoskeletal-associated protein (Arc) expression was induced in sham- and ADX-dependent animals during the conditioning phase, Arc and early growth response 1 (Egr-1) induction was restricted to sham-dependent rats following memory retrieval. Moreover, we found a correlation between Arc induction and CPA score, and Arc was selectively expressed in the granular zone of the DG in dopaminoceptive, glutamatergic and GABAergic neurons. We further found that brain-derived neurotrophic factor was regulated in the opposite way during the test phase. Our results also suggest a role for epigenetic regulation on the expression of glucocorticoid receptors and Arc following memory retrieval. Our data provide the first evidence that GC homeostasis is important for the expression of long-term morphine-withdrawal memories. Moreover, our results support the idea that targeting Arc and Egr-1 in the DG may provide important insights into the role of these signaling cascades in withdrawal-context memory re-consolidation. Together, disrupting these processes in the DG might lead to effective treatments in drug addiction thereby rapidly and persistently reducing invasive memories and subsequent drug seeking.
  • Thumbnail Image
    Publication
    Open Access
    Morphometric evidence of the regulation of the activity of LH-immunoreactive cells by corticosterone. An in vivo and in vitro study
    (Murcia : F. Hernández, 1996) Rubio, M.; Carretero, J.; Cabo, J.J.; Santos, M.; Vázquez, R.J.; Vázquez, R.; Sánchez, F.
    The present study was performed to investigate the morphometric effects of the administration of corticosterone on LH-immunoreactive cells of pituitary monolayer cultures. In addition, the effect of bilateral adrenalectomy on the LH-adenohypophyseal cells was explored. In vitro administration of corticosterone induced a marked decrease in the morphometric parameters considered (cellular, cytoplasmic and nuclear areas). In vivo, bilateral adrenalectomy produced a significant increase in these parameters when compared to those obtained in normal and sham-operated animals. However, when the bilaterally adrenalectomized rats received a daily dose of corticosterone no significant changes in the morphometric parameters were found. Morphometrically, these combined in vivo-in vitro findings confirm a corticosterone-induced hypoactivity of LI4-cells together with a direct effect of this glucocorticoid on LH-adenohypophyseal cells.
  • Thumbnail Image
    Publication
    Open Access
    Role of glucocorticoids on noradrenergic and dopaminergic neurotransmission within the basolateral amygdala and dentate gyrus during morphine withdrawal place aversion
    (Wiley, 2019-02-19) García Pérez, Daniel; Milanés Maquilón, María Victoria; Farmacología; Facultades de la UMU::Facultad de Medicina
    Aversive memories related to drug withdrawal can generate a motivational state leading to compulsive drug taking. However, the mechanisms underlying the generation of these withdrawal memories remain unclear. Limbic structures, such as the basolateral amygdala (BLA) and the dentate gyrus (DG) of the hippocampus, play a crucial role in the negative affective component of morphine withdrawal. Given the prominent role of glucocorticoids (GCs), noradrenaline (NA), and dopamine (DA) in memory-related processes, in the present study, we employed the conditioned place aversion (CPA) paradigm to uncover the role of GCs on NA and DA neurotransmission within the BLA and NA neurotransmission within the DG during opiate-withdrawal conditioning (memory formation consolidation), and after reexposure to the conditioned environment (memory retrieval). We observed that adrenalectomy impaired naloxone-induced CPA. Memory retrieval was associated with an increase in dihydroxyphenylacetic acid (DOPAC) levels in the BLA in morphine-addicted animals in a GC-independent manner. Importantly, NA turnover was related with the expression of withdrawal physical signs during the conditioning phase and with locomotor activity during the test phase. On the other hand, reduced DA concentration in the BLA was correlated with the CPA score. Our results indicate that while noradrenergic system is more associated with the somatic consequences of withdrawal, dopaminergic neurotransmission modulates the affective state. Nevertheless, it seems necessary that both systems work together with GCs to enable aversive-memory formation and recall.