Restraint stress effects on glutamate signaling protein levels in the rats' frontal cortex: Does β1 adrenoceptor activity matter?

Introduction: Stress-evoked dysfunctions of the frontal cortex (FC) are correlated with changes in the functioning of the glutamatergic system, and evidence demonstrates that noradrenergic transmission is an important regulator of this process. In the current study, we adopted a restraint stress (RS) model in male Wistar rats to investigate whether the blockade of β1 adrenergic receptors (β1AR) with betaxolol (BET) in stressed animals influences the body's stress response and the expression of selected signaling proteins in the medial prefrontal cortex (mPFC).

Methods: The study was divided into two parts.

Psychosocial Crowding Stress-Induced Changes in Synaptic Transmission and Glutamate Receptor Expression in the Rat Frontal Cortex.

This study demonstrates how exposure to psychosocial crowding stress (CS) for 3, 7, and 14 days affects glutamate synapse functioning and signal transduction in the frontal cortex (FC) of rats. CS effects on synaptic activity were evaluated in FC slices of the primary motor cortex (M1) by measuring field potential (FP) amplitude, paired-pulse ratio (PPR), and long-term potentiation (LTP). Protein expression of GluA1, GluN2B mGluR1a/5, VGLUT1, and VGLUT2 was assessed in FC by western blot.

Chronic Isolation Stress Affects Subsequent Crowding Stress-Induced Brain Nitric Oxide Synthase (NOS) Isoforms and Hypothalamic-Pituitary-Adrenal (HPA) Axis Responses.

The nitric oxide (NO) pathway in the brain is involved in response to psychosocial stressors. The aim of this study was to elucidate the role of nNOS and iNOS in the prefrontal cortex (PFC), hippocampus (HIP), and hypothalamus (HYPO) during social isolation stress (IS), social crowding stress (CS), and a combined IS + CS. In the PFC, 3 days of CS increased iNOS but not nNOS protein level.

Chronic social isolation in adaptation of HPA axis to heterotypic stress.

Background: Social crowding and isolation are recognized as major stressors and risk factors for development of psychiatric disorders. Chronic isolation stress (IS) and crowding stress (CS) activate neuroendocrine and neurochemical mechanisms, that activate the hypothalamic-pituitary-adrenal (HPA) axis. Changes of the plasma level of interleukin-1β (IL-1β), ACTH and corticosterone (CORT) after chronic psychosocial IS and CS were investigated.

Nitric Oxide Synthase Inhibitor Attenuates the Effects of Repeated Restraint Stress on Synaptic Transmission in the Paraventricular Nucleus of the Rat Hypothalamus.

Corticotropin-releasing hormone (CRH)-synthesizing parvocellular neuroendocrine cells (PNCs) of the hypothalamic paraventricular nucleus (PVN) play a key role in the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis. Several studies have demonstrated that synaptic inputs to these cells may undergo stress-related enhancement but, on the other hand, it has been reported that exposition to the same stressor for prolonged time periods may induce a progressive reduction in the response of the HPA axis to homotypic stressors. In the present study rats were subjected to 10 min restraint sessions, repeated twice daily for 3 or 7 days.

Psychosocial stress inhibits additional stress-induced hyperexpression of NO synthases and IL-1β in brain structures.

Background: The aim of this study was to compare the expression of interleukin-1β (IL-1β), neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) in the prefrontal cortex (PFC), hippocampus (HIP) and hypothalamus (HT) during chronic crowding (CS) (psychosocial) and restraint (RS) (physico-psychological) stress. Adaptational changes of these stress mediators to a subsequent acute RS, in two models of chronic stress were investigated.

Methods: Rats were crowded (24 in one cage) or restrained in metal tubes for 10min twice a day for 3, 7, and 14 consecutive days and decapitated.

Chronic stress adaptation of the nitric oxide synthases and IL-1β levels in brain structures and hypothalamic-pituitary-adrenal axis activity induced by homotypic stress.

The aim of this study was to determine the effect of repeated restraint stress (RS) on a single restraint (homotypic) stress-induced expression of interleukin-1β (IL-1β), neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) in the prefrontal cortex (PFC), hippocampus and hypothalamus and their adaptational changes in chronic stress. Also the involvement of plasma IL-1β in adrenocorticotropic hormone (ACTH) and corticosterone secretion during chronic stress was investigated. Rats were subjected to a single restraint for 10 minutes or restrained twice a day for 3, 7 and 14 consecutive days and 24 hours after the last stress period rats were restrained for 10 min and rapidly decapitated 0, 1, 2 and 3 hours later.

Cytokines, prostaglandins and nitric oxide in the regulation of stress-response systems.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is accepted as one of the fundamental biological mechanisms that underlie major depression. This hyperactivity is caused by diminished feedback inhibition of glucocorticoid (GC)-induced reduction of HPA axis signaling and increased corticotrophin-releasing hormone (CRH) secretion from the hypothalamic paraventricular nucleus (PVN) and extra-hypothalamic neurons. During chronic stress-induced inhibition of systemic feedback, cytosolic glucocorticoid receptor (GR) levels were significantly changed in the prefrontal cortex (PFC) and hippocampus, both structures known to be deeply involved in the pathogenesis of depression.

Brain nitric oxide synthases in the interleukin-1β-induced activation of hypothalamic-pituitary-adrenal axis.

Background: Interleukin-1β (IL-1β), the major cytokine involved in activation of hypothalamic-pituitary-adrenal (HPA) axis modulates both central and peripheral components regulating HPA activity. The role of nitric oxide (NO) generated by neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) in brain structures involved in HPA axis regulation has not been elucidated. The aim of the study was to assess the receptor selectivity of IL-1β stimulatory action on HPA axis and to determine the involvement of nNOS and iNOS in this stimulation.

Effect of co-treatment with fluoxetine or mirtazapine and risperidone on the active behaviors and plasma corticosterone concentration in rats subjected to the forced swim test.

Background: Several clinical reports have postulated a beneficial effect of the addition of a low dose of risperidone to the ongoing treatment with antidepressants in treatment-resistant depression.

Methods: The present study aimed to examine the effect of treatment with fluoxetine or mirtazapine, given separately or jointly with risperidone, on active behavior and plasma corticosterone level in male Wistar rats subjected to the forced swim test (FST).

Results: The obtained results showed that fluoxetine (5 mg/kg), mirtazapine (5 and 10 mg/kg) or risperidone (0.

Effect of repeated restraint on homotypic stress-induced nitric oxide synthases expression in brain structures regulating HPA axis.

Background: Restraint stress (RS) markedly increases interleukin 1-β (IL-1β) generation in brain structures involved in hypothalamic-pituitary adrenocortical (HPA) axis regulation. The IL-1β-induced transient stimulation of HPA axis activity was parallel in time and magnitude to respective changes in regulation of HPA activity. In the present experiment the expression of neuron al and inducible nitric oxide synthase (nNOS and iNOS) were investigated in prefrontal cortex, hippocampus and hypothalamus in response to acute restraint stress in control and prior repeatedly restrained rats.

Effect of prior stress on interleukin-1β and HPA axis responses to acute stress.

Interleukin-1β (IL-1β) level is modulated during multiple stress reactions both in brain structures involved in hypothalamic-pituitary-adrenal (HPA) axis regulation and peripheral systems. Multiple distinct stressors induce different IL-1β and HPA axis responses. The purpose of the present study was to determine if the effect of prior repeated restraint stress on IL-1β levels in prefrontal cortex, hippocampus, hypothalamus and plasma may have an impact on alterations induced in HPA axis responses.

Interleukin-1 (IL-1) in stress-induced activation of limbic-hypothalamic-pituitary adrenal axis.

Proinflammatory cytokine interleukin-1 (IL-1) produced during psychological and immunological stress, plays a significant role in the neuroendocrine and stress responses. Brain IL-1 is an important mediator in stress-induced stimulation of the limbic-hypothalamic-pituitary-adrenal axis and secretion of ACTH and corticosterone. This review aims to describe some signaling pathways between the limbic-hypothalamic-pituitary structures during prolonged stress responses including their sensitization and adaptation.

Prostaglandins and interleukin-1beta in the hypothalamic-pituitary-adrenal response to systemic phenylephrine under basal and stress conditions.

We investigated the role of interleukin-1beta (IL-1beta) and prostaglandins (PG) in the alpha(1)-adrenergic agonist, phenylephrine-induced hypothalamic-pituitary-adrenal axis (HPA) responses under basal and social stress conditions. Male Wistar rats, either control or exposed to crowding stress for 7 days prior to treatment, were used in these experiments. All compounds were injected i.

Nitric oxide in the adrenergic-and CRH-induced activation of hypothalamic-pituitary-adrenal axis.

In this report we investigated the effect of 7-nitroindazole (7-NI), a specific neuronal inhibitor of nitric oxide synthase (nNOS) and L-NAME, a nonselective NOS inhibitor upon the adrenergic- and CRH-induced stimulation of the hypothalamic-pituitary-adrenal axis in nonanesthetized rats. 7-NI given i.p.

Nitric oxide and prostaglandins in the clenbuterol-induced ACTH and corticosterone secretion.

The present study was designed to determine the involvement of nitric oxide (NO) and prostaglandins (PG) in the stimulatory action of clenbuterol, a selective beta(2)-adrenergic receptor agonist on hypothalamic-pituitary-adrenal (HPA) axis under basal and social crowding stress conditions. Clenbuterol given i.c.

Effect of subdiaphragmatic vagotomy and cholinergic agents in the hypothalamic-pituitary-adrenal axis activity.

In the present study, we examined whether the vagus nerve is involved in mediating the stimulation of hypothalamic-pituitary-adrenal (HPA) axis by cholinergic muscarinic and nicotinic agonists, carbachol and nicotine. The site of HPA axis muscarinic stimulation was determined using peripheral (i.p.

The involvement of nitric oxide and prostaglandins in the cholinergic stimulation of hypothalamie-pituitary-adrenal response during crowding stress.

The aim of the present study was to determine the effect of social crowding stress and significance of nitric oxide (NO) and prostaglandins (PG) generated by constitutive and inducible nitric oxide synthase (NOS) and cyclooxygenase (COX) in the stimulation of hypothalamic-pituitary-adrenal (HPA) axis by cholinergic muscarinic receptor agonist carbachol. Inhibitors of neuronal NOS (nNOS) L-NNA, general NOS L-NAME and inducible NOS (iNOS) aminoguanidine, as well as inhibitors of COX-1, piroxicam, and COX-2, compound NS-398 were administered 15 min prior to carbachol to control or crowded rats (24 rats in cage for 7, during 3 and 7 days). In stressed rats L-NAME, L-NNA and aminoguanidine significantly intensified the carbachol-induced ACTH and corticosterone secretion, like in control rats.

Nitric oxide mediates the interleukin-1beta- and nicotine-induced hypothalamic-pituitary-adrenocortical response during social stress.

We investigated the role of nitric oxide (NO) in the interleukin 1beta (IL-1beta) and nicotine induced hypothalamic-pituitary-adrenal axis (HPA) responses, and a possible significance of CRH and vasopressin in these responses under basal and social stress conditions. Male Wistar rats were crowded in cages for 7 days prior to treatment. All compounds were injected i.

Psychosocial stress affects the involvement of prostaglandins and nitric oxide in the lipopolysaccharide-induced hypothalamic-pituitary-adrenal response.

The role of prostaglandins and nitric oxide (NO), generated after peripheral lipopolysaccharide (LPS) administration, in the adaptation of hypothalamic-pituitary-adrenal (HPA) axis under stressful circumstances remains to be elucidated. The aim of the present study was to assess the effect of chronic repetitive restraint or social crowding stress on the involvement of nitric oxide and prostaglandins in the LPS-induced pituitary-adrenocortical response. Male Wistar rats were restrained in metal tubes 2 x 10 min/day or crowded in cages for 7 days prior to treatment.

Nitric oxide and prostaglandin systems in the stimulation of hypothalamic-pituitary-adrenal axis by neurotransmitters and neurohormones.

The review presents our results on the regulatory role of prostaglandins (PG) and nitric oxide (NO) in the activation of hypothalamic-pituitary-adrenal (HPA) axis by cholinergic, adrenergic and histaminergic systems and by neurohormones: corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) under basal conditions. The synthesis of endogenous PG or NO was inhibited by non-selective and selective cyclooxygenase (COX) antagonists and nitric oxide synthase (NOS) blockers given 15 min before the respective receptor agonist and HPA axis activity was assessed 1 h later by measuring plasma ACTH and serum corticosterone levels. The muscarinic agent - carbachol-induced HPA response was considerably supressed by piroxicam, a predominantly constitutive cyclooxygenase (COX-1) inhibitor and significantly diminished by indomethacin, a non-selective COX blocker, but was unaffected by compound NS-398, an inducible cyclooxygenase (COX-2) antagonist.

Role of prostaglandins and nitric oxide in the lipopolysaccharide-induced ACTH and corticosterone response.

This study was designed to determine the role of endogenous prostaglandins (PG) and nitric oxide (NO) in the lipopolysaccharide (LPS)-induced ACTH and corticosterone secretion in conscious rats. LPS (0.5 and 1 mg/kg) given i.

Role of nitric oxide in the nicotine-induced pituitary-adrenocortical response.

Nitric oxide (NO) is a major signaling molecule and biological mediator of the hypothalamic-pituitary-adrenal (HPA) axis. We investigated the role of NO formed by endothelial (e), neuronal (n) and inducible (i) nitric oxide synthase (NOS) in the stimulatory effect of nicotine on the HPA axis in rats under basal conditions. Also possible interaction of NOS systems with endogenous prostaglandins (PG) in that stimulation was assessed.

Influence of cyclooxygenase inhibitors on the central histaminergic stimulations of hypothalamic - pituitary - adrenal axis.

Brain histamine participates in central regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Endogenous prostaglandins modulate signal transduction of different neurotransmitters involved in activation of HPA axis. In the present experiment we investigated whether endogenous prostaglandins are involved in the stimulation of ACTH and corticosterone secretion by histaminergic systems in the rat brain.