5-MeO-DMT induces sleep-like LFP spectral signatures in the hippocampus and prefrontal cortex of awake rats.

5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a potent classical psychedelic known to induce changes in locomotion, behaviour, and sleep in rodents. However, there is limited knowledge regarding its acute neurophysiological effects. Local field potentials (LFPs) are commonly used as a proxy for neural activity, but previous studies investigating psychedelics have been hindered by confounding effects of behavioural changes and anaesthesia, which alter these signals. To address this gap, we investigated acute LFP changes in the hippocampus (HP) and medial prefrontal cortex (mPFC) of freely behaving rats, following 5-MeO-DMT administration. 5-MeO-DMT led to an increase of delta power and a decrease of theta power in the HP LFPs, which could not be accounted for by changes in locomotion. Furthermore, we observed a dose-dependent reduction in slow (20-50 Hz) and mid (50-100 Hz) gamma power, as well as in theta phase modulation, even after controlling for the effects of speed and theta power. State map analysis of the spectral profile of waking behaviour induced by 5-MeO-DMT revealed similarities to electrophysiological states observed during slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. Our findings suggest that the psychoactive effects of classical psychedelics are associated with the integration of waking behaviours with sleep-like spectral patterns in LFPs.

Enhancing anaerobic digestion of automotive paint sludge through biochar addition.

The reduction of traditional fuel sources and the unpredictability of the global economy have led to a push for renewable energy alternatives. Waste recycling can significantly reduce greenhouse gas emissions. In this study, the effects of different proportions of biochar on the efficiency of mesophilic anaerobic digestion of automotive paint sludge were investigated over a period of one month. A combination of paint sludge and anaerobic sludge in a ratio of three to one was used, and biochar was added to the anaerobic digestion reactor in two different amounts of 10 and 26 g/l, with a control sample without biochar. The cumulative volume of biogas produced at the end of the one-month experiment was recorded for three samples: the control sample (without biochar), the second sample (with 2 g of biochar), and the third sample (with 5.2 g of biochar). The volumes of biogas produced were 300, 380, and 530 ml, respectively. Additionally, the COD reduction rates were 25%, 33%, and 48%, and the VS decrement rates were 21%, 27%, and 43%, respectively. The findings showed that adding biochar to the anaerobic digestion reactor containing automotive paint sludge increased biogas production. Additionally, gas chromatography results for an optimal sample of biogas extracted from the anaerobic digestion reactor indicated the presence of about 50% methane gas. These results highlight the potential for utilizing biochar in anaerobic digestion processes to improve renewable energy production and waste management.

A Review on Biomedical Application of Polysaccharide-Based Hydrogels with a Focus on Drug Delivery Systems.

Over the last years of research on drug delivery systems (DDSs), natural polymer-based hydrogels have shown many scientific advances due to their intrinsic properties and a wide variety of potential applications. While drug efficacy and cytotoxicity play a key role, adopting a proper DDS is crucial to preserve the drug along the route of administration and possess desired therapeutic effect at the targeted site. Thus, drug delivery technology can be used to overcome the difficulties of maintaining drugs at a physiologically related serum concentration for prolonged periods. Due to their outstanding biocompatibility, polysaccharides have been thoroughly researched as a biological material for DDS advancement. To formulate a modified DDS, polysaccharides can cross-link with different molecules, resulting in hydrogels. According to our recent findings, targeted drug delivery at a certain spot occurs due to external stimulation such as temperature, pH, glucose, or light. As an adjustable biomedical device, the hydrogel has tremendous potential for nanotech applications in involved health areas such as pharmaceutical and biomedical engineering. An overview of hydrogel characteristics and functionalities is provided in this review. We focus on discussing the various kinds of hydrogel-based systems on their potential for effectively delivering drugs that are made of polysaccharides.

Investigation on factors associated with ovarian cancer: an umbrella review of systematic review and meta-analyses.

Following cervical and uterine cancer, ovarian cancer (OC) has the third rank in gynecologic cancers. It often remains non-diagnosed until it spreads throughout the pelvis and abdomen. Identification of the most effective risk factors can help take prevention measures concerning OC. Therefore, the presented review aims to summarize the available studies on OC risk factors. A comprehensive systematic literature search was performed to identify all published systematic reviews and meta-analysis on associated factors with ovarian cancer. Web of Science, Cochrane Library databases, and Google Scholar were searched up to 17th January 2020. This study was performed according to Smith et al. methodology for conducting a systematic review of systematic reviews. Twenty-eight thousand sixty-two papers were initially retrieved from the electronic databases, among which 20,104 studies were screened. Two hundred seventy-seven articles met our inclusion criteria, 226 of which included in the meta-analysis. Most commonly reported genetic factors were MTHFR C677T (OR=1.077; 95 % CI (1.032, 1.124); P-value<0.001), BSML rs1544410 (OR=1.078; 95 %CI (1.024, 1.153); P-value=0.004), and Fokl rs2228570 (OR=1.123; 95 % CI (1.089, 1.157); P-value<0.001), which were significantly associated with increasing risk of ovarian cancer. Among the other factors, coffee intake (OR=1.106; 95 % CI (1.009, 1.211); P-value=0.030), hormone therapy (RR=1.057; 95 % CI (1.030, 1.400); P-value<0.001), hysterectomy (OR=0.863; 95 % CI (0.745, 0.999); P-value=0.049), and breast feeding (OR=0.719, 95 % CI (0.679, 0.762) and P-value<0.001) were mostly reported in studies. Among nutritional factors, coffee, egg, and fat intake significantly increase the risk of ovarian cancer. Estrogen, estrogen-progesterone, and overall hormone therapies also are related to the higher incidence of ovarian cancer. Some diseases, such as diabetes, endometriosis, and polycystic ovarian syndrome, as well as several genetic polymorphisms, cause a significant increase in ovarian cancer occurrence. Moreover, other factors, for instance, obesity, overweight, smoking, and perineal talc use, significantly increase the risk of ovarian cancer.

Yarrowia lipolytica Bioprocess Development: From Flask to Bioreactor.

Yarrowia lipolytica produces a range of valuable biotechnological products from natural metabolites and enzymes to heterologous proteins. The production of these products is affected by medium composition and various environmental factors. Here we describe bioprocess development for a recombinant laccase production by Y. lipolytica. At first, response surface methodology (RSM), as a statistical technique for design of experiment (DOE), is used for the optimization of medium composition in flask level. Then, results of RSM are applied to increase laccase production in controlled conditions of the bioreactor.

Alterations in brainstem auditory processing, the acoustic startle response and sensorimotor gating of startle in Wistar audiogenic rats (WAR), an animal model of reflex epilepsies.

While acute audiogenic seizures in response to acoustic stimulus appear as an alteration in sensory-motor processing in the brainstem, the repetition of the stimulus leads to the spread of epileptic activity to limbic structures. Here, we investigated whether animals of the Wistar Audiogenic Rat (WAR) strain, genetically selected by inbreeding for seizure susceptibility, would have alterations in their auditory response, assessed by the auditory brainstem responses (ABR) and sensory-motor gating, measured as pre-pulse inhibition (PPI), which could be related to their audiogenic seizures susceptibility or severity. We did not find differences between the amplitudes and latencies of ABR waves in response to clicks for WARs when compared to Wistars. Auditory gain and symmetry between ears were also similar. However, hearing thresholds in response to some tones were lower and amplitudes of wave II were larger in WARs. WARs had smaller acoustic startle reflex amplitudes and the percentages of startle inhibited by an acoustic prepulse were higher for WARs than for Wistars. However, no correlation was found between these alterations and brainstem-dependent seizure severity or limbic seizure frequency during audiogenic kindling. Our data show that while WARs present moderate alterations in primary auditory processing, the sensory motor gating measured in startle/PPI tests appears to be more drastically altered. The observed changes might be correlated with audiogenic seizure susceptibility but not seizures severity.

Naloxone-precipitated withdrawal ameliorates impairment of cost-benefit decision making in morphine-treated rats: Involvement of BDNF, p-GSK3-ß, and p-CREB in the amygdala.

Several studies indicated that morphine administration impairs cognitive brain functions. Therefore, in the current study, we investigated the effect of subchronic exposure to morphine and its withdrawal on effort- and/or delay-based forms of cost-benefit decision making and alterations in p-CREB/CREB ratio, p-GSK3ß/GSK3ß ratio, and BDNF level during decision making in the amygdala. Our data displayed an impairment of both forms of cost-benefit decision making following subchronic exposure to morphine. However, preference of high reward/high effort and/or high delay reward increased after naloxone injection. In molecular section, levels of BDNF and p-CREB/CREB ratio increased during cost-benefit decision making while p-GSK3ß/GSK3ß ratio decreased in both forms of decision making. In morphine-treated rats, level of BDNF and p-CREB/CREB ratio reduced during both forms of decision making while p-GSK3ß/GSK3ß ratio increased during delay-based and did not have a significant difference with the control group during effort-based decision making. On the withdrawal day, BDNF level raised while p-GSK3ß/GSK3ß ratio attenuated compared to morphine-treated group in both form of decision making. In addition, p-CREB/CREB ratio increased only during delay-based decision making on the withdrawal day. In conclusion, our data revealed that subchronic exposure to morphine interferes with the cost-benefit decision making may be via changes in level of BDNF, p-CREB/CREB and p-GSK3ß/GSK3ß ratio in the amygdala.

Laccase production from sucrose by recombinant Yarrowia lipolytica and its application to decolorization of environmental pollutant dyes.

Laccases are used in decolorization and biodegradation of synthetic dyes, bioremediation of industrial wastewaters and delignification of lignocellulosic compounds. The aims of the present study were the optimization of a recombinant laccase production in Yarrowia lipolytica yeast using sucrose as a main carbon source, and the application of the resulting enzyme to decolorization of synthetic dyes, which are problematic environmental pollutants. Taguchi's experimental design method was employed to optimize medium compounds. Recombinant laccase production by Y. lipolytica YL4 strain increased to 900 U L-1 after optimization of sucrose, ammonium chloride, yeast extract and thiamine levels in the modified PPB medium. Furthermore, the production rate reached 6760 U L-1 in a 5 L bioreactor which represents 4.5- and 33.5-fold increases compared to cultures that were in shake-flask with optimized and primary media, respectively. The supernatant containing secreted recombinant laccase was applied for decolorization of seven dyes. The effects of pH, the amount of enzyme and incubation period were verified. The effect of incubation time on dye decolorization by recombinant laccase was important, which has an influence of greater extent than 90% after 48 h for all dyes. The Trametes versicolor laccase can be efficiently produced in Y. lipolytica and the recombinant enzyme has a considerable potential in the decolorization of pollutant synthetic dyes.

Role of D1-like and D2-like dopamine receptors within the ventral tegmental area in stress-induced and drug priming-induced reinstatement of morphine seeking in rats.

The ventral tegmental area (VTA) as a major source of dopamine neurons projecting to cortical and limbic regions has a crucial role in reward as well as stress processes. Dopamine is a predominant neurotransmitter in the reward system, which plays an important role in both drug priming-induced and cue-induced reinstatement of cocaine and heroin seeking. It has been shown that this neurotransmitter has a role in stress-induced relapse to drug seeking. Therefore, the present study aims to evaluate the effects of intra-VTA administration of SCH-23390, as a dopamine D1-like receptor antagonist, and sulpiride, as a dopamine D2-like receptor antagonist, on drug priming-induced and food deprivation (FD)-induced reinstatement. The rats were bilaterally implanted by two separate cannulae into the VTA. After the acquisition and extinction of morphine-conditioned place preference, the animals received different doses of SCH-23390 or sulpiride (0.15, 0.4, 1.5 and 4 mg/0.3 µl vehicle per side) into the VTA on the reinstatement day and tested for drug priming-induced reinstatement of morphine (1 mg/kg) or FD-induced reinstatement facilitated by an ineffective dose of morphine (0.5 mg/kg) in separate groups. Our findings indicated that the D1/D2-like receptor antagonists attenuated the drug priming-induced and FD-induced reinstatement. However, these decrements were more significant in groups of animals that received a 24-h FD as a stressor. The data may suggest a role for the VTA dopaminergic system in relapse to drugs of abuse, which may be induced either by re-exposure to morphine or exposure to a stressor.

Microinjection of the mGluR2/3 agonist, LY379268, into the nucleus accumbens attenuates extinction latencies and the reinstatement of morphine-induced conditioned place preference in rats.

Previous studies indicate that metabotropic glutamate receptor type 2/3 (mGluR2/3) has a key role in the rewarding properties of morphine-induced conditioning place preference (CPP). Group II mGluR2/3 agonists are offered as a drug addiction treatment. The nucleus accumbens (NAc), which is one of the important areas involved in the reward circuitry, also expresses these receptors. In this study, we evaluated the effects of mGluR2/3 agonist, LY379268, on the extinction and reinstatement of morphine-induced CPP, following its microinjection into the NAc. Adult male Wistar rats (220-250 g) were implanted bilaterally by two separate cannulae into the NAc. After the acquisition of morphine CPP, different doses of LY379268 (0.3, 1 and 3 µg/0.5 µl saline) were microinjected into the NAc every day during the extinction period and, in a different set of experiments, on the reinstatement test day, 60 min before the infusion of a priming dose of morphine (1 mg/kg; subcutaneous). Thereafter, the animals were tested for place preference by the Ethovision software. The intra-accumbal injection of the mGluR2/3 agonist, LY379268, significantly decreased the extinction latencies and reinstatement of morphine-induced CPP at higher doses. It seems that the NAc might be a functional region for mGluR2/3 to play a regulatory role for decreasing drug-seeking behavior in rats. Furthermore, it can be said that mGluR2/3 agonists have a potential role in the treatment of drug-seeking behaviors.

Production of Laccase by Recombinant Yarrowia lipolytica from Molasses: Bioprocess Development Using Statistical Modeling and Increase Productivity in Shake-Flask and Bioreactor Cultures.

Laccases are used in numerous applications, from green degradation of various xenobiotic compounds, waste detoxification, textile dye bleaching, and delignification of lignocellulose materials to biofuel production. In this study, the recombinant Yarrowia lipolytica YL4 strain carrying the white-rot fungus Trametes versicolor laccase IIIb gene was used for laccase production from beet molasses as an agro-industrial residue. Response surface methodology was used to statistical optimization of the production of laccase by Y. lipolytica using an industrial medium containing molasses which allows a six times increase in laccase activity compared to primary medium contains glucose after 144 h. In bioreactor cultivation after 48 h, laccase production reached to 3.7- and 22.5-fold more than optimized and primary media in shake-flask cultures, respectively. Laccase productivity in bioreactor (0.0937 U/h) was higher than shake-flask culture (0.0084 U/h). The present study provides valuable information about statistical optimization of bioprocess development for cost-effective production of laccase and other heterologous proteins in Y. lipolytica from beet molasses as sole carbon source, thus allowing the valorization and decreasing environmental pollution of this agro-industrial waste.

Administration of activated glial condition medium in the nucleus accumbens extended extinction and intensified reinstatement of methamphetamine-induced conditioned place preference.

Methamphetamine (METH) is a psychostimulant drug with significant abuse potential and neurotoxic effects. A high percentage of users relapse to use after detoxification and no effective medication has been developed for treatment of METH addiction. Developing evidences indicated the role of glial cells in drugs abused related phenomena. However, little is known about the role of these cells in the maintenance and reinstatement of METH-seeking behaviors. Therefore, the current study was conducted to clarify the role of glial cells in the maintenance and reinstatement of METH-induced conditioned place preference (CPP) in rats. Astrocyte condition medium (ACM) and neuroglia conditioned medium (NCM) are liquid mediums prepared from primary astrocyte and neuroglia cells. These mediums seem to contain many factors that release by glia cells. CPP was induced by systemic administration of METH (1mg/kg for 5days, s.c.). Following the establishment of CPP, the rats were given daily bilateral injections (0.5µl/side) of either vehicle, ACM or NCM into the nucleus accumbens (NAc) and then were tested for the maintenance and reinstatement. Intra-NAc administration of ACM treated with METH, could extend the extinction period and also, intensified the magnitude of METH reinstatement. Furthermore, intra-accumbal administration of NCM treated with METH notably delayed the extinction period by four days and significantly increased the magnitude of CPP score in the reinstatement phase compared to the post-test phase. Collectively, these findings suggested that activation of glial cells may be involved in the maintenance and reinstatement of METH-seeking behaviors. It provides new evidence that glia cells might be considered as a potential target for the treatment of METH addiction.

Involvement of orexin-1 and orexin-2 receptors within the dentate gyrus of the hippocampus in the acquisition, expression and extinction of lateral hypothalamic-induced conditioned place preference in the rats.

Orexinergic projections originating from the lateral hypothalamus (LH) have an important role in the acquisition of the LH-stimulation conditioned place preference (CPP). Among the brain areas associated with reward processing, LH orexinergic neurons send projections to the dentate gyrus (DG) region of the hippocampus, and it has been shown that orexin receptors are expressed in the DG. In this study, we investigated the role of intra-DG orexin-1 (OX1) and orexin-2 (OX2) receptors on acquisition, expression and extinction of CPP induced by stimulation of the LH. Rats were unilaterally implanted by two separate cannulae into the LH and DG. The CPP paradigm was done; conditioning scores and locomotor activities were recorded by Ethovision software. The results showed that intra-DG administration of SB334867, a selective OX1r antagonist, and TCS OX2 29, a selective OX2r antagonist, (0.5, 5, 12.5 and 50nM/0.5µl DMSO) before carbachol microinjection (250nM; effective dose) during the 3-days conditioning phase, dose-dependently inhibited the development of LH stimulation-induced CPP in the rats. However, this reduction in OX1r antagonist treated groups was more than that in OX2r antagonist treated animals. In addition, these antagonists decreased the expression of LH-induced CPP. Moreover, OX1r but not OX2r antagonist could shorten the extinction duration of place preference. We conclude that the orexinergic projections from the LH to DG are involved in the development, expression and extinction of CPP induced by LH stimulation.

Intra-accumbal Orexin-1 Receptors are Involved in Antinociception Induced by Stimulation of the Lateral Hypothalamus in the Formalin Test as an Animal Model of Persistent Inflammatory Pain.

Orexin, mainly produced by orexin-expressing neurons in the lateral hypothalamus (LH), plays an important role in pain modulation. Moreover, it is shown that the nucleus accumbens (NAc) is one of the important areas involved in this modulation. Orexin-1 (OX1) and orexin-2 (OX2) receptors are densely distributed in the NAc. The study investigated the involvement of OX1 receptors in the NAc on antinociception induced by intra-LH administration of carbachol in formalin test. Rats were unilaterally implanted by two separate cannulae into the LH and NAc. Different doses of SB334867, as an OX1 receptor antagonist, were microinjected into the NAc (1, 3 and 10 nM/0.5 µL DMSO) prior to intra-LH carbachol injection (250 nM/0.5 µL saline). Formalin test was applied as an animal model of persistent inflammatory pain. The animals received a subcutaneous injection of formalin into the hind paw, 5 min after SB334867 administration. Pain scores were calculated at 5-min blocks for a 60-min test period. Results showed that the administration of SB334867 into the NAc decreased LH chemical stimulation-induced antinociception dose-dependently in early and second phase of formalin test. Our findings showed that OX1 receptors in the NAc may be involved in modulation of inflammatory pain.

Functional interaction between OX2 and CB1 receptors in the ventral tegmental area and the nucleus accumbens in response to place preference induced by chemical stimulation of the lateral hypothalamus.

Orexinergic projections derived from the lateral hypothalamus (LH) to the ventral tegmental area (VTA) and the nucleus accumbens (NAc), play a key role in the acquisition of conditioned place preference (CPP) induced by LH stimulation. On the other hand, there are several studies which support the idea of the existence of a cross-talk between the orexinergic and cannabinoid systems. Nevertheless, the function and how both systems interact in the reward circuit remain unknown. In this study, the authors tried to clarify the role of orexin-2 receptor (OX2r) within the VTA and NAc in the development of reward-related behaviors after chemical stimulation of the LH and also find out the involvement of CB1 cannabinoid receptors in this phenomenon. Animals were implanted by two separate cannulae into the LH and VTA or NAc, unilaterally. The CPP paradigm was done; and conditioning scores were recorded. The results showed that administration of TCS OX2 29 as a selective OX2r antagonist (1, 3 and 10 nM/rat) into the VTA or NAc just 5 min before microinjection of carbachol (250 nM/0.5 µl saline), a cholinergic agonist, into the LH during the 3-day conditioning phase, could dose-dependently inhibit the development of LH stimulation-induced CPP. Furthermore, concurrent injection of ineffective doses of TCS OX2 29 and AM251, as a CB1 receptor antagonist, into the NAc could reduce conditioning scores. The findings of this study showed that the OX2 receptor has a critical role in modulating reward circuit in the VTA and NAc, when the LH was stimulated by carbachol. Moreover, we suggest the existence of an interaction between orexinergic and cannabinoid systems within the VTA and NAc in place preference induced by LH stimulation.

Role of dopamine D2-like receptors within the ventral tegmental area and nucleus accumbens in antinociception induced by lateral hypothalamus stimulation.

Several lines of evidence have shown that stimulation of the lateral hypothalamus (LH) can induce antinociception. It has been indicated that hypothalamic orexinergic neurons send projections throughout the dopamine mesolimbic pathway. Functional interaction between the LH and the main area of the mesolimbic pathway such as the ventral tegmental area (VTA) and the nucleus accumbens (NAc) implicates in pain modulation. Thus, in this study, we investigated the role of D2-like dopamine receptors within the VTA and NAc in the LH stimulation-induced antinociception. Male Wistar rats weighing 230-280 g were unilaterally implanted with two separate cannulae into the LH and VTA or NAc. Animals received intra-VTA (0.25, 1 and 4 µg/0.3 µl DMSO) and intra-accumbal (0.125, 0.25, 1 and 4 µg/0.5 µl DMSO) infusions of sulpiride as a selective D2-like receptor antagonist, prior to intra-LH carbachol (125 nM/rat) administration. In the tail-flick test, the antinociceptive effects were measured using a tail-flick algesiometer and represented as maximal possible effect (%MPE) within 5, 15, 30, 45 and 60 min after injections. Our results showed that intra-VTA and intra-accumbal sulpiride dose-dependently attenuated the LH stimulation-induced antinociception. However, the blockade of D2-like receptors within the NAc was more significant than that of the VTA. These findings show that D2-like dopamine receptors in these regions play an important role in the LH-mediated modulation of nociceptive information in the acute model of pain in the rats. It seems that this pain modulating system is more relevant to D2-like receptors in the nucleus accumbens.

Blockade of D1-like dopamine receptors within the ventral tegmental area and nucleus accumbens attenuates antinociceptive responses induced by chemical stimulation of the lateral hypothalamus.

It was established that stimulation of the lateral hypothalamus (LH) can induce antinociception. Previous studies showed a role for the ventral tegmental area (VTA) and nucleus accumbens (NAc) in antinociception induced by LH stimulation through the orexinergic system. In this study, we tried to assess the involvement of dopamine D1-like receptors within the VTA and NAc in the LH stimulation-induced antinociception. Male Wistar rats were unilaterally implanted with two separate cannulae into the LH and VTA or NAc. Animals received intra-VTA or intra-accumbal infusion of SCH-23390, as a D1-like dopamine receptor antagonist (0.125, 0.25, 1 and 4 µg/rat), 2 min before intra-LH administration of carbachol (125 nM/rat). The antinociceptive effects of SCH-23390 were measured by using a tail-flick analgesiometer and represented as maximal possible effect (%MPE). Results showed that intra-VTA and/or accumbal administration of SCH-23390 could prevent carbachol-induced antinociception. These findings revealed that D1-like dopamine receptors within the VTA and NAc play an important role in antinociceptive effect induced by chemical stimulation of the LH.

Functional interaction between the orexin-1 and CB1 receptors within the nucleus accumbens in the conditioned place preference induced by the lateral hypothalamus stimulation.

Several studies have shown that chemical stimulation of the lateral hypothalamus (LH) by carbachol induces the conditioned place preference (CPP) in rats. LH is the main source of the orexinergic neurons and sends projections to some areas of the brain such as the nucleus accumbens (NAc). We tried to determine the role of intra-accumbal orexin-1 (OX1) receptors in development (acquisition) and expression of reward-related behaviors induced by LH stimulation and involvement of CB1 cannabinoid receptors in this area. Adult male Wistar rats were unilaterally implanted by two separate cannulae into the LH and NAc. The CPP paradigm was done; conditioning scores and locomotor activities were recorded. The results showed that intra-accumbal administration of SB334867 as a selective OX1 receptor antagonist (1, 3, 10 and 30nM/0.5µl DMSO) 5min before intra-LH carbachol (250nM/0.5µl saline) during 3-day conditioning phase, could dose-dependently inhibit the development of LH-induced CPP. In expression experiments, intra-NAc administration of SB334867 on the test day could decrease the expression of LH stimulation-induced CPP. Furthermore, concurrent intra-accumbal administration of effective/ineffective doses of SB334867 and AM251 (45 and 15µM) as a CB1 receptor antagonist, before carbachol during the conditioning phase, could attenuate the development of LH stimulation-induced CPP. It seems that the orexinergic projection from the LH to the NAc is involved in the LH stimulation-induced CPP and OX1 receptor in the NAc has a substantial role in this phenomenon. Our findings also suggest the existence a functional interaction between OX1 and CB1 receptors within the NAc in place preference.

The potential role of regenerative medicine in the man-agement of traumatic patients.

Traumatic injury represents the most common cause of death in ages 1 to 44 years and asignificant proportion of patients treated in hospital emergency wards each year. Unfortunately, for patients who survive their injuries, survival is not equal to complete recovery. Many traumatic injuries are difficult to treat with conventional therapy and result in permanent disability. In such situations, regenerative medicine has the potential to play an important role in recovery of function. Regenerative medicine is a field that seeks to maintain or restore function with the development of biological substitutes for diseased or damaged tissues. Several regenerative approaches are currently under investigation, with a few achieving clinical application. For example, engineered skin has gained FDA approval, and more than 20 tissue engineered skin substitutes are now commercially available. Other organ systems with promising animal models and small human series include the central and peripheral nervous systems, the musculoskeletal system, the respiratory and genitourinary tracts, and others. This paper will be a clinically oriented review of the regenerative approaches currently under investigation of special interest to those caring for traumatic patients.

Role of intra-hippocampal orexin 1 and orexin 2 receptors in conditioned place preference induced by chemical stimulation of the lateral hypothalamus.

Evidence from animal models suggests a role for orexinergic system in reward processing and drug addiction. The lateral hypothalamus (LH) orexin neurons send projections to the dorsal hippocampus (CA1 region) which plays a pivotal role in reward processes. Moreover, it has been shown that orexin containing terminals and orexin receptors are distributed in the hippocampal formation. In this study, we assessed the role of orexin 1 (OX1r) and orexin2 (OX2r) receptors in the CA1 on the development of LH stimulation-induced conditioned place preference (CPP). Animals weighing 230-280 g were unilaterally implanted by two separate cannulae into the LH and CA1. The CPP paradigm was done; SB334867 and TCSOX229, as selective OX1r and OX2r antagonists (1, 3, 10 and 30 nM/0.5 µl DMSO) administrated into the CA1 prior to intra-LH carbachol microinjection (250 nM; the most effective dose) during the 3-days conditioning phase, respectively. Conditioning scores and locomotor activities were recorded by Ethovision software on the test day. The results showed that the administration of OX1r and OX2r antagonists into the CA1 attenuated the development of CPP induced by chemical stimulation of the LH. However, this decrease in OX1r antagonist treated groups was more significant than that in OX2r antagonist treated animals. Our findings suggest that OX1 and OX2 receptors in the CA1 region of the hippocampus were involved in the development of CPP induced by chemical stimulation of the LH and the efficiency of OX1 receptors in this phenomenon was more considerable than OX2 receptors in rats.