The role of stress in drug addiction is well established. negative affective states withdrawal most probably involve recruitment brain neurocircuitry [e.g., induction hypothalamo-pituitary-adrenocortical (HPA) axis, noradrenergic activity, and corticotropin-releasing factor (CRF) activity]. present study investigated t$he CRF receptor-1 subtype (CRF1R) on the response system to morphine withdrawal. effects naloxone-precipitated noradrenaline (NA) turnover paraventricular nucleus (PVN), HPA...

Both the hypothalamus-pituitary-adrenal (HPA) axis and extrahypothalamic brain stress system are key elements of neural circuitry that regulates negative states during abstinence from chronic drug exposure. Orexins have recently been hypothesized to modulate extended amygdala contribute emotional state associated with dependence. This study examined impact morphine withdrawal on lateral hypothalamic (LH) orexin A (OXA) gene expression activity as well OXA involvement in response abstinence....

Adverse early-life conditions induce persistent disturbances that give rise to negative emotional states. Therefore, early life stress confers increased vulnerability substance use disorders, mainly during adolescence as the brain is still developing. In this study, we investigated consequences of maternal separation, a model neglect, on psychotropic effects cocaine and neuroplasticity dopaminergic system. Our results show mice exposed separation displayed attenuated behavioural...

Morphine withdrawal results in serious affective and somatic symptoms including activation of the hypothalamo-pituitary-adrenocortical (HPA) axis. To reveal secretory, activational transcriptional changes hypothalamus morphine-dependent rats during naloxone precipitated opioid withdrawal, we measured corticosterone secretion, c-Fos induction heteronuclear (hn)RNA levels corticotropin-releasing hormone (CRH) arginine vasopressin (AVP) naïve morphine dependent animals injected with saline or 5...

The modification in the activity of noradrenergic neurons projecting to hypothalamus and pituitary-adrenal response during morphine withdrawal as well its correlation with alterations corticotropin-releasing factor (CRF) vasopressin (AVP) content different brain areas was analyzed. Male rats were implanted placebo (naïve) or (tolerant/dependent) pellets for 7 days. On day 8, groups received an acute injection saline s.c. (control) naloxone (1 mg/kg s.c.) decapitated 30 min later. After...

Chronic opiate exposure induces neurochemical adaptations in the noradrenergic system. Enhanced responsiveness of hypothalamo-pituitary-adrenal axis after morphine withdrawal has been associated with hyperactivity ascending input from nucleus solitary tract (NTS-A2) cell group to hypothalamic paraventricular (PVN). This study addressed role withdrawal-induced corticosterone (CORT) release regulation tyrosine hydroxylase (TH), rate-limiting enzyme catecholamine biosynthesis adrenalectomized...

The transcription factor DeltaFosB is induced in the nucleus accumbens (NAc) by drugs of abuse. This study was designed to evaluate possible modifications FosB/DeltaFosB expression both hypothalamic and extrahypothalamic brain stress system during morphine dependence withdrawal. Rats were made dependent on and, day 8, injected with saline or naloxone. Using immunohistochemistry western blot, FosB/DeltaFosB, tyrosine hydroxylase (TH), corticotropin-releasing (CRF) pro-dynorphin (DYN) measured...

Chronic use of drugs abuse profoundly alters stress-responsive system. Repeated exposure to morphine leads accumulation the transcription factor ΔFosB, particularly in brain areas associated with reward and stress. The persistent effects ΔFosB on target genes may play an important role plasticity induced by abuse. Recent evidence suggests that stress-related hormones (e.g., glucocorticoids, GC) induce adaptations stress system is likely involve alteration gene expression factors. This study...

Epigenetic changes such as microRNAs (miRs)/Ago2-induced gene silencing represent complex molecular signature that regulate cellular plasticity. Recent studies showed involvement of miRs and Ago2 in drug addiction. In this study, we show expression induced by morphine withdrawal occur with concomitant epigenetic modifications the mesolimbic dopaminergic (DA) pathway [ventral tegmental area (VTA)/nucleus accumbens (NAc) shell], which is critically involved drug-induced dependence. We found...

Different data support a role for brainstem noradrenergic inputs to the hypothalamic paraventricular nucleus (PVN) in control of hypothalamus – pituitary adrenocortical (HPA) axis. However, little is known regarding functional adaptive changes afferent innervating PVN and supraoptic (SON) during chronic opioid exposure upon morphine withdrawal. Here we have studied expression Fos after administration withdrawal rat SON. production was also regions that innervate nuclei: solitary tract (NTS A...

Abstract We previously demonstrated that morphine withdrawal induced hyperactivity of noradrenergic pathways innervating the hypothalamic paraventricular nucleus (PVN) in rats, parallel with an increase neurosecretory activity hypothalamus–pituitary–adrenocortical (HPA) axis, as evaluated by corticosterone release. These neuroendocrine effects were dependent on stimulation α‐adrenoceptors. In present study, Fos immunostaining was used a reflection neuronal and combined for tyrosine...

Previous research has shown an increase in hypothalamo-pituitary-adrenal axis activity following naloxone administration to morphine-dependent rats. In the present study, we investigated adaptive changes noradrenaline (NA) and dopamine (DA) systems hypothalamic paraventricular nucleus (PVN) during morphine dependence withdrawal. Additionally, examined possible change 3′,5′-cyclic adenosine monophosphate (cAMP) levels that under same conditions. Rats were made dependent on by or placebo...

Our previous studies have shown that naloxone-induced morphine withdrawal increases the hypothalamic-pituitary-adrenocortical (HPA) axis activity, which is dependent on a hyperactivity of noradrenergic pathways [nucleus tractus solitarius (NTS) A2] innervating hypothalamic paraventricular nucleus (PVN). Short-term regulation catecholamine biosynthesis occurs through phosphorylation tyrosine hydroxylase (TH), enhances enzymatic activity. In present study, effect site-specific TH in PVN and...

Exposure to drugs of abuse or stress results in adaptation the brain involving changes gene expression and transcription factors. Morphine withdrawal modulates through various second-messenger signal transduction systems. Here, we investigated activation factor, cAMP-response element binding protein (CREB), hypothalamic paraventricular nucleus (PVN) kinases that may mediate morphine withdrawal-triggered CREB response hypothalamic-pituitary-adrenocortical (HPA) axis after naloxone-induced...

Background Extinction period of positive affective memory drug taking and negative withdrawal, as well the different response men women might be important for clinical treatment addiction. We investigate role corticotropin releasing factor receptor type one (CRF1R) male female mice in expression extinction aversive memory. Methodology/Principal Finding used genetically engineered lacking functional CRF1R. The animals were rendered dependent on morphine by intraperitoneally injection...

Administration of the preferential μ-opioid receptor agonist, morphine, and selective κ-opioid agonists elicits activation hypothalamus-pituitary-adrenocortical axis, although site or molecular mechanisms for these effects have not been determined. The expression Fos, protein product c-fos protooncogene, has widely used as an anatomical marker monitoring neuronal activity. In present study we evaluated 1) those trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl-]benzeneacetamide...

In humans, remifentanil anesthesia enhances nociceptive sensitization in the postoperative period. We hypothesized that activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) expression c-Fos, prodynorphin (mRNA), dynorphin spinal cord could participate molecular mechanisms underlying opioid-induced sensitization. a mouse model incisional pain, we evaluated thermal (Hargreaves test) mechanical (von Frey) hyperalgesia during first 21 days. Moreover, (mRNA, real-time polymerase...

Recent evidence suggests that corticotropin-releasing factor (CRF) receptor signalling is involved in modulating the negative symptoms of opiate withdrawal. In this study, a series experiments were performed to further characterize role CRF-type 2 (CRF₂) withdrawal-induced physical signs dependence, hypothalamus-pituitary-adrenal (HPA) axis activation, enhanced noradrenaline (NA) turnover hypothalamic paraventricular nucleus (PVN) and tyrosine hydroxylase (TH) phosphorylation (activation),...

Stress induces the release of peptide corticotropin-releasing factor (CRF) into ventral tegmental area (VTA), and also increases dopamine (DA) levels in brain regions receiving dense VTA input. Since role stress drug addiction is well established, present study examined possible involvement CRF1 receptor interaction between morphine withdrawal catecholaminergic pathways reward system. The effects naloxone-precipitated on signs withdrawal, hypothalamo-pituitary-adrenocortical (HPA) axis...