Socially defeated male rats display a blunted adrenocortical response to a low dose of 8-OH-DPAT

The study examined in male Wistar rats the influence of social defeat on the neuroendocrine stress response system using injection of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), as the pharmacological challenge. Social defeat was defined by the submissive postures displayed by the Wistar rats which were threatened and attacked by Tryon Maze Dull S3 rats for 10 min. 18-20 h after social defeat, the defeated rats were injected intravenously (i.v.) with a low and high dose of 8-OH-DPAT in their home cages. Blood samples were withdrawn from the freely moving cannulated rats for determination of plasma corticosterone and catecholamines. The corticosterone response to the low dose of 8-OH-DPAT (0.05 mg/kg, i.v.) was significantly diminished in the defeated rats as compared to the controls, but this dose failed to affect catecholamine concentrations. The high dose of 8-OH-DPAT (0.15 mg/kg, i.v.) significantly elevated corticosterone and adrenaline levels in defeated and control rats to the same extent, whereas no effect on noradrenaline was found. The present data thus indicate that social defeat blunts 5-HT1A receptor-mediated adrenocortical activation probably via a decrease in the sensitivity of a population of postsynaptic 5-HT receptors

Polycomb Binding Precedes Early-Life Stress Responsive DNA Methylation at the Avp Enhancer

Early-life stress (ELS) in mice causes sustained hypomethylation at the downstream Avp enhancer, subsequent overexpression of hypothalamic Avp and increased stress responsivity. The sequence of events leading to Avp enhancer methylation is presently unknown. Here, we used an embryonic stem cell-derived model of hypothalamic-like differentiation together with in vivo experiments to show that binding of polycomb complexes (PcG) preceded the emergence of ELS-responsive DNA methylation and correlated with gene silencing. At the same time, PcG occupancy associated with the presence of Tet proteins preventing DNA methylation. Early hypothalamic-like differentiation triggered PcG eviction, DNA-methyltransferase recruitment and enhancer methylation. Concurrently, binding of the Methyl-CpG-binding and repressor protein MeCP2 increased at the enhancer although Avp expression during later stages of differentiation and the perinatal period continued to increase. Overall, we provide evidence of a new role of PcG proteins in priming ELS-responsive DNA methylation at the Avp enhancer prior to epigenetic programming consistent with the idea that PcG proteins are part of a flexible silencing system during neuronal development

Coordinative Mineralocorticoid and Glucocorticoid Receptor-Mediated Control of Responses to Serotonin in Rat Hippocampus

In a previous study we showed that selective occupation of the mineralocorticoid receptor (MR) in hippocampal slices from adrenalectomized (ADX) rats attenuates the membrane hyperpolarization and resistance decrease induced in CA1 pyramidal neurons by serotonin (5HT). In the present study we established responses to 5HT in the hippocampal slice when not only MRs but also glucocorticoid receptors (GRs) were occupied, using either a combination of selective MR and GR ligands or different concentrations of the endogenous mixed agonist corticosterone. We observed that the GR agonist RU 28362 blocks the attenuating action of the MR agonist aldosterone on responses to 3, 10 and 30-mu-M 5HT; RU 28362 by itself did not affect 5HT responses. If a low concentration of the mixed agonist corticosterone (0.5 nM, close to the Kd for the MR) was continuously perfused in vitro, 5HT responses were steadily depressed with a delay of 2 h, while high levels of corticosterone (5 nM, around Kd for GR) only temporarily reduced 5HT responses. Finally, 5HT responses in slices from sham-operated rats (with relatively high plasma corticosterone levels) were similar to the responses obtained in slices from ADX rats. These data suggest that the previously reported MR-mediated attenuation of 5HT responses may be limited to conditions of low adrenocortical activity or pathophysiological conditions where the balance of MR- and GR-mediated effects is disturbed

Control of neuronal excitability by corticosteroid hormones

The rat adrenal hormone corticosterone can cross the blood-brain barrier and bind to two intracellular receptor populations in the brain - the mineralocorticoid and glucocorticoid receptor. Recent studies have revealed that the corticosteroid hormones are able to restore changes in neuronal membrane properties induced by current or neurotransmitters, probably through a genomic action. In general, mineralocorticoid receptors mediate steroid actions that enhance cellular excitability, whereas activated glucocorticoid receptors can suppress temporarily raised neuronal activity. The steroid-mediated control of excitability and the implications for information processing in the brain are reviewed in this article

Effect of corticosteroid hormones on electrical activity in rat hippocampus

Pyramidal neurons in the rat CA1 hippocampal area contain both mineralocorticoid (MR) and glucocorticoid receptors (GR) which bind the endogenous adrenal steroid corticosterone with differential affinity. With intracellular electrophysiological recording techniques we have investigated how corticosterone affects the membrane properties of these cells. We observed that low doses (1 nM) of corticosterone or aldosterone can, through MR, reduce the spike frequency accommodation and afterhyperpolarization (AHP) evoked by a short depolarizing current in pyramidal neurons. As the accommodation/AHP can be considered as an intrinsic mechanism of CA1 neurons to attenuate transmission of excitatory input, the MR-mediated action might potentially enhance cellular excitability in the CA1 area. Higher doses of corticosterone or selective glucocorticoids were able to reverse the MR-mediated effect on accommodation/AHP, eventually increasing particularly the amplitude of the AHP. GR-mediated events may thus potentially suppress excitability in the hippocampal CA1 area. Not only current- but also transmitter-induced membrane effects were affected by the steroids. Firstly, GR-ligands were able to suppress a temporary noradrenaline-evoked decrease in accommodation/AHP. Secondly, membrane hyperpolarizations induced by serotonin were reduced by MR-agonists. We propose that cellular excitability in the hippocampus is at least partly under control of coordinative, antagonistic MR- and GR-mediated effects on electrical activity

Mineralocorticoid hormones suppress serotonin-induced hyperpolarization of rat hippocampal CA1 neurons

Pyramidal neurons in the rat CA 1 hippocampal area contain intracellular mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) to which the adrenal hormone corticosterone can bind with differential affinity. The pyramidal neurons also have high amounts of 5-HT1a receptors, which mediate a membrane hyperpolarization. With intracellular recording in vitro, we found that selective occupation of MRs suppresses the 5-HT-induced hyperpolarization of CA 1 pyramidal neurons. The suppression of 5-HT responses was observed 1-4 hr after a brief (20-min) application of the steroids. Binding properties of the 5-HT1a receptor were not significantly affected by in vitro steroid application. Furthermore, responses to the GABA(B) agonist baclofen were not changed after treatment with MR ligands, implying that the K+ conductance to which both GABA(B) and 5-HT1a receptors are linked is also no target for the steroid action. The MR-mediated effect on 5-HT responsiveness potentially enhances cellular activity. Because activation of GRs was previously found to suppress norepinephrine-induced excitability in the same neurons, the data support the concept that cellular homeostasis in the hippocampus is under control of corticosterone via coordinative, antagonistic MR- and GR-mediated events

Omvårdnadsprogrammet i relation till hemtjänstarbete

Av omvårdnadspersonalen inom äldreomsorgen saknar fyra av tio formell yrkesutbildning för sitt arbete. Eftersom hemtjänstpersonalens arbetsuppgifter innefattar såväl hushållsarbete, att vårda svårt sjuka och döende personer, människor med olika grad av psykisk sjukdom, missbruk som olika typer av funktionshinder, bör utbildningen möta detta kompetensbehov. Syftet med studien är att undersöka hur vårdbiträden som har gått omvårdnadsprogrammet upplever att den kunskap och kompetens de skaffat sig under utbildningstiden kommer till användning i hemtjänstarbetet. Metoden som använts är en kvalitativ intervjustudie, där 11 personer som genomgått omvårdnadsprogrammets utbildning intervjuats. Respondenterna är fördelade på sex hemtjänstlag. Vid analysen av intervjuerna kategoriserades materialet på följande sätt: Arbetsinnehåll, Kunskapsbehov i hemtjänsten samt Tillämplighet av omvårdnadsprogrammets innehåll i hemtjänsten. Resultatet visar att de flesta av respondenterna upplevde att utbildningen var bra och tillförde mycket som de har nytta av i sitt arbete, men den påvisar även vissa brister i relation till hemtjänstarbetet. Exempelvis upplevs kunskaperna i psykiatri som bristfälliga. Studien visar också att respondenterna är medvetna om den sociala och existentiella dimensionen i sitt arbete genom att de ofta i sina svar återkom till bemötandefrågor. Flera av respondenterna som läst kursen Social omsorg framhåller den bland de kurser som de har mest nytta av i sitt dagliga arbete. Med utgångspunkt från det resultat studien visar, skulle vissa kurser behöva läggas till och då främst kurser i psykiatri och socialpsykiatri samt att kursen social omsorg bör vara obligatorisk