Az ecstasy hatása a kognitív funkciókra

Az ecstasy főleg entaktogén és eufóriát okozó hatásai miatt közkedvelt kábítószer a fiatalok körében. Akutan az ecstasy a visszavételi mechanizmusok megfordításával megemeli az agyi monoaminok koncentrációját és ezen keresztül fokozza az ébrenlétet, emeli a testhőmérsékletet, valamint csökkenti az agyi vérátáramlást és a táplálékfelvételt. Hosszú távon ugyanakkor az agyi szerotonin koncentrációk és szerotonerg markerek mennyiségének csökkenése figyelhető meg a felhasználókban. Ezzel párhuzamosan funkcionális károsodások is megjelenhetnek, mint például az alvás- és hangulatzavarok, valamint a szorongás és az agresszivitás fokozódása. Mindemellett az ecstasy egyik legjellemzőbb hosszú távú mellékhatása a kognitív deficit. Különösen a szert rendszeresen fogyasztó felhasználók esetén csökkent retro- és prospektív memória, valamint károsodott végrehajtó funkciók figyelhetők meg. Számos tanulmány a szerotonerg károsodás mellett felvetette az endokannabinoid rendszer, az alvásszabályzás és a hypothalamus-hypophysis-mellékvesekéreg tengely szerepét e folyamatban. Ugyanakkor ismert, hogy a fenti rendszerek egymás működését is képesek befolyásolni. Jelen tanulmányunkban a szerotonerg károsodás, az endokannabinoid rendszer és a fenti szabályozó mechanizmusok hatásait külön-külön, valamint egymásra gyakorolt lehetséges interakcióikat is tárgyaljuk, amelyek magyarázhatják az ecstasy által okozott hosszan tartó kognitív funkciócsökkenést

Nesfatin-1/NUCB2 as a Potential New Element of Sleep Regulation in Rats.

STUDY OBJECTIVES: Millions suffer from sleep disorders that often accompany severe illnesses such as major depression; a leading psychiatric disorder characterized by appetite and rapid eye movement sleep (REMS) abnormalities. Melanin-concentrating hormone (MCH) and nesfatin-1/NUCB2 (nesfatin) are strongly co - expressed in the hypothalamus and are involved both in food intake regulation and depression. Since MCH was recognized earlier as a hypnogenic factor, we analyzed the potential role of nesfatin on vigilance. DESIGN: We subjected rats to a 72 h-long REMS deprivation using the classic flower pot method, followed by a 3 h-long 'rebound sleep'. Nesfatin mRNA and protein expressions as well as neuronal activity (Fos) were measured by quantitative in situ hybridization technique, ELISA and immunohistochemistry, respectively, in 'deprived' and 'rebound' groups, relative to controls sacrificed at the same time. We also analyzed electroencephalogram of rats treated by intracerebroventricularly administered nesfatin-1, or saline. RESULTS: REMS deprivation downregulated the expression of nesfatin (mRNA and protein), however, enhanced REMS during 'rebound' reversed this to control levels. Additionally, increased transcriptional activity (Fos) was demonstrated in nesfatin neurons during 'rebound'. Centrally administered nesfatin-1 at light on reduced REMS and intermediate stage of sleep, while increased passive wake for several hours and also caused a short-term increase in light slow wave sleep. CONCLUSIONS: The data designate nesfatin as a potential new factor in sleep regulation, which fact can also be relevant in the better understanding of the role of nesfatin in the pathomechanism of depression

Acute escitalopram treatment inhibits REM sleep rebound and activation of MCH-expressing neurons in the lateral hypothalamus after long term selective REM sleep deprivation.

RATIONALE: Selective rapid eye movement sleep (REMS) deprivation using the platform-on-water ("flower pot") method causes sleep rebound with increased REMS, decreased REMS latency, and activation of the melanin-concentrating hormone (MCH) expressing neurons in the hypothalamus. MCH is implicated in the pathomechanism of depression regarding its influence on mood, feeding behavior, and REMS. OBJECTIVES: We investigated the effects of the most selective serotonin reuptake inhibitor escitalopram on sleep rebound following REMS deprivation and, in parallel, on the activation of MCH-containing neurons. METHODS: Escitalopram or vehicle (10 mg/kg, intraperitoneally) was administered to REMS-deprived (72 h) or home cage male Wistar rats. During the 3-h-long "rebound sleep", electroencephalography was recorded, followed by an MCH/Fos double immunohistochemistry. RESULTS: During REMS rebound, the time spent in REMS and the number of MCH/Fos double-labeled neurons in the lateral hypothalamus increased markedly, and REMS latency showed a significant decrease. All these effects of REMS deprivation were significantly attenuated by escitalopram treatment. Besides the REMS-suppressing effects, escitalopram caused an increase in amount of and decrease in latency of slow wave sleep during the rebound. CONCLUSIONS: These results show that despite the high REMS pressure caused by REMS deprivation procedure, escitalopram has the ability to suppress REMS rebound, as well as to diminish the activation of MCH-containing neurons, in parallel. Escitalopram caused a shift from REMS to slow wave sleep during the rebound. Furthermore, these data point to the potential connection between the serotonergic system and MCH in sleep regulation, which can be relevant in depression and in other mood disorders

Az ecstasy hatasa a kognitiv funkciokra.

The recreational drug ecstasy is widely used among dance clubbers for its acute euphoric and entactogenic effects. Ecstasy exerts its acute effects by increasing the extracellular concentration of monoamines in the brain by reversing the functions of reuptake mechanisms. These elevations in extracellular monoamine concentrations result in wake promoting effects, body hyperthermia and reductions in local cerebral blood flow. However, on the long-run, ecstasy reduces serotonin concentration and density of serotonergic markers in several brain areas. Functional deficits, like sleep disturbances, anxiogenic- and aggressive behavioral responses and mood disorders also may occur. However, one of the most prominent adverse effects is related to the cognitive functions. Following ecstasy use attenuated retro- and prospective memory and defective higher order cognitive functions can be observed, especially in heavy users. Several studies indicated the involvement of the endocannabinoid system, the sleep regulating centers and the hypothalamic-pituitary-adrenal axis based on or parallel to serotonergic damage in these processes. Recent evidence, however, also showed that changes in one of the latter systems can influence the functions of each other. In this review we summarize the related literature, and propose a complex mechanism for the long-lasting cognitive deficits following heavy ecstasy use

Dehydroepiandrosterone Pretreatment Alters the Ischaemia/Reperfusion-Induced VEGF, IL-1 and IL-6 Gene Expression in Acute Renal Failure

Background: Beneficial effects of dehydroepiandrosterone (DHEA) pretreatment were reported in ischaemia/reperfusion (I/R)-induced kidney damage. Methods: To investigate the mechanism of DHEA pretreatment during renal I/R injury, the left renal pedicles of DHEA- [G(DHEA); 4.0 mg/kg/day DHEA dissolved in propylene glycol (PG)] and PG-pretreated male Wistar rats (G(PG)) were clamped for 55 min followed by 2 (T-2) and 24 h (T-24) of reperfusion. Sham-operated, non-clamped animals (T-0) served as controls in both groups. Renal function, kidney morphology and interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) expression were determined in the kidneys of both groups. Results: Renal functional parameters and kidney structure did not differ in G(DHEA) versus G(PG) at any time point. Renal mRNA expression of IL-1 beta was lower at T-0, while IL-6 at T-2 was lower in G(DHEA) than in G(PG). While renal VEGF mRNA expression remained unchanged, protein levels were increased at T-2 and T-24 compared to T-0 kidneys in both groups. VEGF protein levels were lower at T-2 and T-24 in G DHEA than in GPG. Conclusion: We found that DHEA pretreatment alters renal IL-1 beta, IL-6 and VEGF synthesis. Moreover, contrary changes in VEGF mRNA and protein levels suggest that VEGF synthesis - distinct from other organs - might be primarily posttranscriptionally regulated in postischaemic rat kidneys. Copyright (C) 2009 S. Karger AG, Base

Effects of intracerebroventricularly administered nesfatin-1 on slow wave sleep and passive wake (PW) vigilance stages.

<p>The time spent and the number of episodes in light slow wave sleep (SWS1, <b>A</b> and <b>D</b>, respectively), deep slow wave sleep (SWS2, <b>B</b> and <b>E</b>, respectively) as well as in PW (<b>C</b> and <b>F</b>, respectively), per hour in the 2^nd–6^th hours of passive (light) phase. Data are presented as mean ± SEM, n = 6 per group, p*<0.05, p**<0.01.</p