Glucocorticoids Regulation of FosB/ΔFosB Expression Induced by Chronic Opiate Exposure in the Brain Stress System

Abstract

Chronic use of drugs of abuse profoundly alters stress-responsive system. Repeated exposure to morphine leads to accumulation of the transcription factor ΔFosB, particularly in brain areas associated with reward and stress. The persistent effects of ΔFosB on target genes may play an important role in the plasticity induced by drugs of abuse. Recent evidence suggests that stress-related hormones (e.g., glucocorticoids, GC) may induce adaptations in the brain stress system that is likely to involve alteration in gene expression and transcription factors. This study examined the role of GC in regulation of FosB/ΔFosB in both hypothalamic and extrahypothalamic brain stress systems during morphine dependence. For that, expression of FosB/ΔFosB was measured in control (sham-operated) and adrenalectomized (ADX) rats that were made opiate dependent after ten days of morphine treatment. In sham-operated rats, FosB/ΔFosB was induced after chronic morphine administration in all the brain stress areas investigated: nucleus accumbens(shell) (NAc), bed nucleus of the stria terminalis (BNST), central amygdala (CeA), hypothalamic paraventricular nucleus (PVN) and nucleus of the solitary tract noradrenergic cell group (NTS-A2). Adrenalectomy attenuated the increased production of FosB/ΔFosB observed after chronic morphine exposure in NAc, CeA, and NTS. Furthermore, ADX decreased expression of FosB/ΔFosB within CRH-positive neurons of the BNST, PVN and CeA. Similar results were obtained in NTS-A2 TH-positive neurons and NAc pro-dynorphin-positive neurons. These data suggest that neuroadaptation (estimated as accumulation of FosB/ΔFosB) to opiates in brain areas associated with stress is modulated by GC, supporting the evidence of a link between brain stress hormones and addiction.

Seasonal decrease in thermogenesis and increase in vasoconstriction explain seasonal response to N6‐cyclohexyladenosine‐induced hibernation in the Arctic ground squirrel (Urocitellus parryii)

“…S2b). The neuroanatomical distribution of TH + neurons in AGS is the same as the distribution reported in rats using the same antibody () in both the NTS (García‐Pérez et al, ) and LC, where specificity was confirmed by TH downregulation experiments (Khanday et al, ). TPH‐ir was detected in the rPA (box3, Fig.…”

Withdrawal induces distinct patterns of FosB/∆FosB expression in outbred Swiss mice classified as susceptible and resistant to ethanol-induced locomotor sensitization

“…Nonetheless, to be technically precise, we will refer in the present study as FosB/DeltaFosB expression. It is important to note that this strategy has been used in others studies, including those that used the same primary antibody described here (Conversi et al, 2008;Li et al, 2010;Flak et al, 2012;García-Pérez et al, 2012). As a consequence, besides these experimental limitations, we will discuss our results considering the role of DeltaFosB in neuronal plasticity.…”

Acute and chronic stress differentially regulate cyclin-dependent kinase 5 in mouse brain: implications to glucocorticoid actions and major depression

“… 29 , 30 Amplification was performed in a three-step cycle: 95 °C for 10 min, then 40 cycles of the reaction consisting of denaturing at 95 °C for 15 s and annealing/extension at 60 °C for 1 min, followed by a melting curve analysis. Ten target genes, which are reported to be glucocorticoid-responsive and/or regulated by stressful stimuli (glucocorticoid-responsive/stress-related genes) were the arginine vasopressin ( AVP ), 31 brain-derived neurotrophic factor ( BDNF ), 32 , 33 corticotropin-releasing hormone ( CRH ), 31 , 34 FBJ murine osteosarcoma viral oncogene homolog ( cFos ), 35 FOSB/ΔFOSB , 36 5-hydroxytryptamine (serotonin) receptor 1A ( HTR1A ), 37 inhibitor of DNA-binding 3 ( ID3 ), 38 nischarin, 39 nuclear speckle splicing regulatory protein 1 ( NSRP1 ), 40 protein phosphatase 1 regulatory subunit 10 ( PPP1R10 ) 41 and serum/glucocorticoid-regulated kinase 1 ( SGK1 ). 42 Primer pairs used in SYBR Green real-time PCR were designed so that the sequence spanning between a foward and a reverse primer contains at least one intron.…”