Effect of microelectrophoretically applied corticosterone on raphe neurones in the rat

doi:10.1016/0304-3940(84)90504-4

Neuroscience Letters

Volume 50, Issues 1–3, 7 September 1984, Pages 307-311

https://doi.org/10.1016/0304-3940(84)90504-4 Get rights and content

Abstract

The effect of microelectrophoretic application of corticosterone (CS) on single neurones of raphe nuclei (RN) were investigated in rats under urethane anaesthesia. Ejecting currents generally ranged from 5 to 40 nA. CS produced an excitatory effect in 61% and no effect in 39% of the neurones. None of the 54 neurones studied was inhibited by CS. These quite homogeneous data support the hypothesis that RN are involved in the regulation of most of the nervous functions in which glucocorticoid hormones have been implicated.

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The review integrates different experimental approaches including biochemistry, c-Fos expression, microdialysis (glutamate, GABA, noradrenaline and serotonin), electrophysiology and fMRI to better understand the effect of elevated level of glucocorticoids on the brain activity and metabolism. The available data indicate that glucocorticoids alter the dynamics of neuronal activity leading to context-specific changes including both excitation and inhibition and these effects are expected to support the task-related responses. Glucocorticoids also lead to diversification of available sources of energy due to elevated levels of glucose, lactate, pyruvate, mannose and hydroxybutyrate (ketone bodies), which can be used to fuel brain, and facilitate storage and utilization of brain carbohydrate reserves formed by glycogen. However, the mismatch between carbohydrate supply and utilization that is most likely to occur in situations not requiring energy-consuming activities lead to metabolic stress due to elevated brain levels of glucose. Excessive doses of glucocorticoids also impair the production of energy (ATP) and mitochondrial oxidation. Therefore, glucocorticoids have both adaptive and maladaptive effects consistently with the concept of allostatic load and overload.
Corticosterone microinjected into nucleus pontis oralis increases tonic immobility in rats
2011, Hormones and Behavior
Citation Excerpt :
With this perspective, CORT secretion could correlate inversely to the proximity with predator and explain our results; a positive modulator role for CORT on TI expression and involve PnO as a part of such mechanism. In spite of the low expression of glucocorticoid receptors in pons (Aronsson et al., 1988; Joëls and de Kloet, 1994), their functional presence has been evidenced in electrophysiological studies; neurons in brainstem, i.e. in raphe nuclei (Avanzino et al., 1984) or pontine region (Dubrovsky et al., 1985) were predominantly excited by local injection of CORT. The current behavioral results also showed the presence of functional corticosteroid receptors in the pons, specifically in PnO.
Tonic immobility (TI) is also known as “immobility response”, “immobility reflex”, “animal hypnosis”, etc. It is an innate antipredatory behavior characterized by an absence of movement, varying degrees of muscular activity, and a relative unresponsiveness to external stimuli. Experimentally, TI is commonly produced by manually forcing an animal into an inverted position and restraining it in that position until the animal becomes immobile. Part of the neural mechanism(s) of TI involves the medullo-pontine reticular formation, with influence from other components of the brain, notably the limbic system. It has been observed that TI is more prolonged in stressed animals, and systemic injection of corticosterone (CORT) also potentiates this behavior. At present, the anatomical brain regions involved in the CORT modulation of TI are unknown. Thus, our study was made to determine if some pontine areas could be targets for the modulation of TI by CORT. A unilateral nucleus pontis oralis (PnO) microinjection of 1 μL of CORT (0.05 μg/1 μL) in rats resulted in clear behavioral responses. The animals had an increased duration of TI caused by clamping the neck (in this induction, besides of body inversion and restraint, there is also clamping the neck), with an enhancement in open-field motor activity, which were prevented by pretreatment injection into PnO with 1 μL of the mineralocorticoid-receptor antagonist spironolactone (0.5 μg/1 μL) or 1 μL of the glucocorticoid-receptor antagonist mifepristone (0.5 μg/1 μL). In contrast, these behavioral changes were not seen when CORT (0.05 μg/1 μL) was microinjected into medial lemniscus area or paramedian raphe. Our data support the idea that, in stressful situations, glucocorticoids released from adrenals of the prey reach the PnO to produce a hyper arousal state, which in turn can prolong the duration of TI.
Rapid corticosteroid actions on behavior: Mechanisms and implications
2009, Hormones, Brain and Behavior Online
The effects of non-genomic glucocorticoid mechanisms on bodily functions and the central neural system. A critical evaluation of findings
2008, Frontiers in Neuroendocrinology
Citation Excerpt :
In the case of such divergences, the rapid non-genomic effects of glucocorticoids were mostly stimulatory in nature, whereas the genomic effects were inhibitory. Such differences in acute and long-term effects were noticed in the case of serotonergic neurotransmission [5,114,121], Ca2+ uptake [168,184], locomotion [85,149,150], sexual behavior [92,116] and aggression [97,116,119]. It worth to mention, however, that these conclusions do not derive from direct comparisons, but from studies performed in different laboratories.
Mounting evidence suggests that—beyond the well-known genomic effects—glucocorticoids affect cell function via non-genomic mechanisms. Such mechanisms operate in many major systems and organs including the cardiovascular, immune, endocrine and nervous systems, smooth and skeletal muscles, liver, and fat cells. Non-genomic effects are exerted by direct actions on membrane lipids (affecting membrane fluidity), membrane proteins (e.g. ion channels and neurotransmitter receptors), and cytoplasmic proteins (e.g. MAPKs, phospholipases, protein kinases, etc.). These actions are mediated by the glucocorticoids per se or by the proteins dissociated from the liganded glucocorticoid receptor complex. The MR and GR also activate non-genomic mechanisms in certain cases. Some effects of glucocorticoids are shared by a variety of steroids, whereas others are more selective. Moreover, “ultra-selective” effects—mediated by certain glucocorticoids only—were also shown. Disparate findings suggest that non-genomic mechanisms also show “demand-specificity”, i.e. require the coincidence of two or more processes. Some of the non-genomic mechanisms activated by glucocorticoids are therapeutically relevant; moreover, the “non-genomic specificity” of certain glucocorticoids raises the possibility of therapeutic applications. Despite the large body of evidence, however, the non-genomic mechanisms of glucocorticoids are still poorly understood. Criteria for differentiating genomic and non-genomic mechanisms are often loosely applied; interactions between various mechanisms are unknown, and non-genomic mechanism-specific pharmacological (potentially therapeutic) agents are lacking. Nevertheless, the discovery of non-genomic mechanisms is a major breakthrough in stress research, and further insights into these mechanisms may open novel approaches for the therapy of various diseases.
The effect glucocorticoids on aggressiveness in established colonies of rats
2007, Psychoneuroendocrinology
Citation Excerpt :
It was suggested that a normal display of offensive aggression is positively related to brief spikes in serotonergic activity, even if a long-lasting serotonergic activation decreases aggressiveness (de Boer and Koolhaas, 2005). Glucocorticoids increase all three dopaminergic (Piazza et al., 1991, 1996; Ronken et al., 1994), noradrenergic (McEwen, 1987; Stone et al., 1987; Roozendaal et al., 2006), and serotonergic (Neckers and Sze, 1975; Avanzino et al., 1984; Laaris et al., 1995; Meijer and de Kloet, 1998) neurotransmission. We hypothesize that glucocorticoids enhance the challenge-induced activation of monoaminergic systems, by which they promote aggressive responses.
It was repeatedly shown that glucocorticoids increase aggressiveness when subjects are socially challenged. However, the interaction between challenge exposure and glucocorticoid effects was not investigated yet. We studied this interaction by assessing the effects of glucocorticoids in established colonies of rats, i.e. in rats that were not exposed to an acute social challenge. Aggressiveness was high immediately after colony formation but decreased sharply within 4 days and remained stable thereafter. Mild dominance relations were observed in 11 colonies (65%). Approximately three weeks after colony formation, rats remained undisturbed or were injected with vehicle or corticosterone. Routine colony life was followed for 1 h after treatments. Injections per se induced a mild and transient behavioral activation: resting was reduced, whereas exploration, social and agonistic interactions were increased. The change lasted about 15 min. Corticosterone—although plasma corticosterone levels were increased—had no specific effect, as the behavior of vehicle- and corticosterone-treated rats was similar. Social rank had a minor impact on the results. In contrast, the pro-aggressive effects of corticosterone were robust under conditions of social challenge and were maintained after repeated exposure to aggressive encounters. It occurs that an acute increase in glucocorticoids promotes social challenge-induced aggressiveness, but does not increase aggressiveness under routine conditions. We hypothesize that the pro-aggressive effects of glucocorticoids develop in conjunction with challenge-induced neuronal (e.g. monoaminergic) activation.
Mechanisms differentiating normal from abnormal aggression: Glucocorticoids and serotonin
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Psychopathology-associated human aggression types are induced by a variety of conditions, are behaviorally variable, and show a differential pharmacological responsiveness. Thus, there are several types of abnormal human aggression. This diversity was not reflected by conventional laboratory approaches that focused on the quantitative aspects of aggressive behavior. Recently, several laboratory models of abnormal aggression were proposed, which mainly model hyperarousal-driven aggressiveness (characteristic to intermittent explosive disorder, post-traumatic stress disorder, depression, chronic burnout, etc.) and hypoarousal-driven aggressiveness (characteristic mainly to antisocial personality disorder and its childhood antecedent conduct disorder). Findings obtained with these models suggest that hyperarousal-driven aggressiveness has at its roots an excessive acute glucocorticoid stress response (and probably an exaggerated response of other stress-related systems), whereas chronic hypoarousal-associated aggressiveness is due to glucocorticoid deficits that affect brain function on the long term. In hypoarousal-driven aggressiveness, serotonergic neurotransmission appears to lose its impact on aggression (which it has in normal aggression), certain prefrontal neurons are weakly activated, whereas the central amygdala (no, or weakly involved in the control of normal aggression) acquires important roles. We suggest that the specific study of abnormal aspects of aggressive behavior would lead to important developments in understanding the specific mechanisms underlying different forms of aggression, and may ultimately lead to the development of better treatment approaches.

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Effect of microelectrophoretically applied corticosterone on raphe neurones in the rat

Abstract

Neurosci. Lett.

Neuropharmacology

Brain Res.

Exp. Neurol.

Exp. Neurol.

Neuroscience

Actions of prostaglandings E1, E2 and F2 on brain stem neurones

Brit. J. Pharmacol. Chemother.

Actions of glucocorticoid hormones on neurones of the rat reticular formation

Neurosci. Lett.

The serotonin-producing neurones of the midbrain median and dorsal raphe nuclei

Species differences in adrenocortical secretion

J. Endocrin.

Spinal and trigeminal mechanisms of nociception

Ann. Rev. Neurosci.

Actions of prostaglandings E₁, E₂ and F₂ on brain stem neurones