Effects of ghrelin on gastric distention sensitive neurons in the arcuate nucleus of hypothalamus and gastric motility in diabetic rats

This study was performed to observe the effects of ghrelin on the activity of gastric distention (GD) sensitive neurons in the arcuate nucleus of hypothalamus (Arc) and on gastric motility in vivo in streptozocin (STZ) induced diabetes mellitus (DM) rats. Electrophysiological results showed that ghrelin could excite GD-excitatory (GD-E) neurons and inhibit GD-inhibitory (GD-I) neurons in the Arc. However, fewer GD-E neurons were excited by ghrelin and the excitatory effect of ghrelin on GD-E neurons was much weaker in DM rats. Gastric motility research in vivo showed that microinjection of ghrelin into the Arc could significantly promote gastric motility and it showed a dose-dependent manner. The effect of ghrelin promoting gastric motility in DM rats was weaker than that in normal rats. The effects induced by ghrelin could be blocked by growth hormone secretagogue receptor (GHSR) antagonist [d-Lys-3]-GHRP-6 or BIM28163. RIA and real-time PCR data showed that the levels of ghrelin in the plasma, stomach and ghrelin mRNA in the Arc increased at first but decreased later and the expression of GHSR-1a mRNA in the Arc maintained a low level in DM rats. The present findings indicate that ghrelin could regulate the activity of GD sensitive neurons and gastric motility via ghrelin receptors in the Arc. The reduced effects of promoting gastric motility induced by ghrelin could be connected with the decreased expression of ghrelin receptors in the Arc in diabetes. Our data provide new experimental evidence for the role of ghrelin in gastric motility disorder in diabetes.     

Ghrelin、GHRP-6以及胃动素对大鼠胃肠运动影响研究

目的:探究ghrelin、GHRP-6以及胃动素对大鼠胃肠运动的影响。方法:在体实验观察ghrelin、GHRP-6及胃动素对大鼠胃排空及小肠推进的影响,离体实验观察ghrelin、GHRP-6及胃动素对大鼠电场刺激引起胃窦胃底平滑肌舒缩反应的影响,RT-PCR观察ghrelin mRNA在胃的表达。结果:在体研究发现ghrelin及GHRP-6能够促进胃排空及小肠推进,胃动素对胃排空及小肠推进无影响。离体研究发现,ghrelin 1μM能够抑制胃底平滑肌4-8Hz开电刺激下的舒张反应,并增强胃底平滑肌1-8Hz及胃窦平滑肌4-16Hz断电刺激下的收缩反应;GHRP-6 1μM能够抑制胃底平滑肌4-8Hz开电刺激下的舒张反应,并增强胃底平滑肌1-2Hz、8-16Hz及胃窦平滑肌4-8Hz断电刺激下的收缩反应;L-NAME增强ghrelin、GHRP-6诱导的胃底和胃窦平滑肌条舒缩作用。大鼠胃窦及胃底分布有ghrelin受体mRNA。结论:ghrelin和GHRP-6能够加快胃排空促进小肠推进,该效应可能是通过迷走神经通路及胆碱能兴奋产生的。     

电刺激大鼠束旁核对底丘脑核和丘脑腹内侧核神经元的影响

本工作旨在探讨电刺激束旁核（parafascicular nucleus,PF）对帕金森病模型（Parkinson’s disease,PD）大鼠神经行为的改善作用及其机制。成年雄性Sprague—Dawley大鼠黑质致密部注射6一羟基多巴胺建立PD大鼠模型。采用行为学方法观察电刺激PF对阿朴吗啡诱发的大鼠旋转行为的作用,并应用在体细胞外记录法观察电刺激PF对大鼠底丘脑核（subthalamic nucleus,STN）及丘脑腹内侧核（ventromedial nucleus,VM）神经元放电的影响。结果发现,高频电刺激（130Hz,0．4mA,5s）PF一周,明显改善PD大鼠旋转行为。细胞外放电记录显示,高频电刺激PF使PD大鼠STN神经元自发放电减少,且该作用具有频率依赖性。另外,高频电刺激PF可使VM神经元兴奋,该作用也是频率依赖性的。我们在实验中同时观察到微电泳谷氨酸（glutamicacid,Glu）受体拮抗剂MK-801使STN神经元放电频率减少或完全抑制,微电泳t氨基丁酸（T-amino butyricacid,GABA）受体拮抗剂印防己毒素（picrotoxin,Pic）则使神经元放电频率增加。以上结果表明,GABA能和GIu能传入纤维可会聚于同-STN神经元,并对后者有紧张性作用。高频刺激PF,使该核团到STN神经元的Glu能兴奋性输出减少,导致STN的失活。这一作用通过基底神经节的间接通路,最终释放了丘脑运动核团VM的活性。高频刺激PF经PF,STN和VM的神经通路而改善PD大鼠神经行为。     

Glutamate release in the ventromedial hypothalamus of the female rat during copulation: Modulation by estradiol

Binding of glutamate or its ionotropic receptor agonists in the ventromedial hypothalamus (VMH) of female rats inhibits both appetitive and consummatory aspects of sexual behavior. Because vaginocervical stimulation activates glutamate neurons in the VMH, and administration of estradiol benzoate (EB) and progesterone (P) delays this effect, the present study examined the effects of hormonal priming on glutamate release within the VMH of female rats paired with sexually vigorous males. Ovariectomized, sexually experienced rats were implanted with guide cannula aimed at the ventrolateral VMH, through which microdialysis probes were inserted prior to testing. Females were assigned randomly to one of three hormone treatment conditions: EB + P, EB alone, or the oil vehicle. Testing was conducted over 5 h, including a 120-min period of habituation to the testing chamber, a 60-min period of baseline sample collection, and a 120-min period during which a sexually vigorous male was introduced into the testing chamber. Dialysates were collected every 20 min during the test and were analyzed for glutamate using HPLC. Females primed with oil had large and significant increases in glutamate release from baseline once the male was introduced to the chamber. Treatment with EB alone decreased glutamate release in response to male cues. Although treatment with EB + P did not differ significantly from EB alone, the degree of reduced glutamate release was less than with EB alone. These results indicate that priming with EB reduces glutamate transmission in the VMH in response to male cues. Taken together with our previous findings, estradiol blunts the activation of glutamate neurons in the VMH thus allowing female rats to copulate.     

Effect of ghrelin on gastric myoelectric activity and gastric emptying in rats

Ghrelin is a recently discovered peptide in the endocrine cells of the stomach, which may stimulate gastric motility via the vagal nerve pathway. However, the mechanism of ghrelin-induced changes in gastrointestinal motility has not been clearly defined. The purpose of this study was to investigate the pharmacological effects of ghrelin on gastric myoelectrical activity and gastric emptying in rats, and to investigate whether cholinergic activity is involved in the effects of ghrelin. The study was performed on Sprague-Dawley rats implanted with serosal electrodes for electrogastrographic recording. Gastric slow waves were recorded from fasting rats at baseline and after injection of saline, ghrelin, atropine, or atropine+ghrelin. Gastric emptying of non-caloric liquid was measured by the spectrophotometric method in conscious rats. Intravenous administration of rat ghrelin (20 microg/kg) increased not only dominant frequency, dominant power and regularity of the gastric slow wave but also the gastric emptying rate when compared with the control rats (P<0.01, P<0.05, P<0.05, P<0.001 respectively). These stimulatory actions of ghrelin on both gastric myoelectrical activity and gastric emptying were not fully eliminated by pretreatment with atropine sulphate. These results taken together suggest that ghrelin may play a physiological role in the enteric neurotransmission controlling gastric contractions in rats.     

Effects of orexins/hypocretins on neuronal activity in the paraventricular nucleus of the thalamus in rats in vitro

Orexin-A (ORX-A) and orexin-B (ORX-B), also called hypocretin-1 and hypocretin-2, respectively, act upon orexin 1 (OX1R) and orexin 2 (OX2R) receptors, and are involved in the regulation of sleep-wakefulness and energy homeostasis. Orexin neurons in the lateral hypothalamic perifornical region project heavily to the paraventricular nucleus of the thalamus (PVT), which is deeply involved in the control of motivated behaviors. In the present study, electrophysiological and cytosolic Ca2+ concentration ([Ca2+]i) imaging studies on the effects of ORX-A and ORX-B on neurons in the PVT were carried out in rat brain slice preparations. ORX-A and/or ORX-B were applied extracellularly in the perfusate. Extracellular recordings showed that about 80% of the PVT neurons were excited dose-dependently by both ORX-A and ORX-B at concentrations of 10(-8) to 10(-6)M, and the increase in firing rate was about three times larger for ORX-B than for ORX-A at 10(-7)M. When both ORX-A and ORX-B were applied simultaneously at 10(-7)M, the increase in firing rate was almost equal to that of ORX-B at 10(-7)M, suggesting that the PVT neurons do not show a high affinity to ORX-A which is expected if they have OX1R receptors. The excitatory effect of ORX-B was seen in low Ca2+ and high Mg2+ ACSF as well as in normal ACSF, and the increase in firing rate was greater in low Ca2+ and high Mg2+ ACSF than in normal ACSF. [Ca2+]i imaging studies demonstrated that [Ca2+]i was increased in about 50% of the PVT neurons by both 10(-7)M ORX-A and ORX-B with a stronger effect for ORX-B, and the increase in [Ca2+]i induced by ORX-B was abolished in Ca2+-free ACSF, suggesting that ORX-B does not release Ca2+ from intracellular Ca2+ stores. Subsequent whole cell patch clamp recordings revealed that an after hyperpolarization seen following each action potential in normal ACSF disappeared in Ca2+-free ACSF, and the mean magnitude of the depolarization induced by ORX-B was same in normal, Ca2+-free and TTX-containing Ca2+-free ACSFs. Furthermore, ORX-B-induced depolarization was reversed to hyperpolarization when membrane potential was lowered to about -97 mV, and an increase of extracellular K+ concentration from 4.25 to 13.25 mM abolished the ORX-B-induced depolarization, indicating that the ORX-B-induced depolarization is associated with an increase in the membrane resistance resulting from a closure of K+ channels. These results suggest that orexins depolarize and excite post-synaptically PVT neurons via OX2R receptors, and that orexin-activated PVT neurons play a role in the integration of sleep-wakefulness and energy homeostasis, and in the control of motivated behaviors.     

GHRP-6 mimics ghrelin-induced stimulation of food intake and suppression of locomotor activity in goldfish

Ghrelin was first identified and characterized from rat stomach as an endogenous ligand for the growth hormone secretagogue (GHS) receptor (GHS-R). Ghrelin also acts as an orexigenic factor and regulates energy balance in rodents. In goldfish, native ghrelin consists of 11 molecular variants, the major form being a 17-residue peptide with n-octanoic acid modification (n-octanoyl ghrelin17), and intraperitoneal (IP) administration of n-octanoyl ghrelin17 induces central actions such as stimulation of food intake and suppression of locomotor activity through capsaicin-sensitive afferents. Four types of GHS-Rs (1a-1, 1a-2, 2a-1 and 2a-2) have been identified in goldfish, and one GHS, GHRP-6, can activate only GHS-R2a-1 in vitro. However, there is no information about the effect of GHRP-6 on food intake and locomotor activity in goldfish in vivo. Therefore, in the present study, we examined whether IP-administered GHRP-6 would mimic the orexigenic action of n-octanoyl ghrelin17 and its suppression of locomotor activity. IP administration of GHRP-6 at 1pmol/g body weight (BW) stimulated food intake, and was equipotent to the orexigenic action of n-octanoyl ghrelin17 at 10 pmol/g BW. IP-injected GHRP-6 at 1 pmol/g BW also induced a significant decrease of locomotor activity, as was the case for IP-injected n-octanoyl ghrelin17 at 10 pmol/g BW. The action of GHRP-6 was blocked by IP-preinjected capsaicin at 160 nmol/g BW. These results suggest that the central action of GHRP-6 might be mediated via the GHS-R2a-1-signaling pathway, and subsequently through capsaicin-sensitive afferents in goldfish.     

Effects of ghrelin on Cx43 regulation and electrical remodeling after myocardial infarction in rats

Ghrelin is a novel growth hormone-releasing peptide, which has been shown to exert beneficial effects on ventricular remodeling. In this study, we investigated whether ghrelin could decrease vulnerability to ventricular arrhythmias in rats with myocardial infarction and the possible mechanism. Twenty-four hours after ligation of the anterior descending artery, adult male Sprague-Dawley rats were randomized to ghrelin (100 μg/kg) and saline (control group) for 4 weeks. Sham animals underwent thoracotomy and pericardiotomy, but not LAD ligation. Myocardial endothelin-1 (ET-1) levels were significantly elevated in saline-treated rats at the border zone compared with sham-operated rats. Myocardial connexin43 (Cx43) expression at the border zone was significantly decreased in saline-treated infarcted rats compared with sham-operated rats. Ghrelin significantly decreased the inducibility of ventricular tachyarrhythmias compared with control group. Arrhythmias sores during programmed stimulation in saline-treated rats were significantly higher than scores in those treated with ghrelin. The electrophysiological improvement of fatal ventricular tachyarrhythmias was accompanied with increased immunofluorescence-stained Cx43, myocardial Cx43 protein and mRNA levels in ghrelin treated rats. We also shown that ghrelin significantly decreased tissue ET-1 levels at the infarcted border zone. Thus, ghrelin showed the protective effect on ventricular arrhythmias after myocardial infarction. Although the precise mechanism by which ghrelin modulates the dephosphorylation of Cx43 remains unknown, it is most likely that the ghrelin increased expression of Cx43 through the inhibition of ET-1.     

Ultrastructure of neurons in the ventromedial nucleus or the hypothalamus in ovariectomized rats with or without estrogen treatment

Summary The fine structure of the ventrolateral and dorsomedial subdivisions of the ventromedial nucleus (VMN) of the hypothalamus was examined in ovariectomized/control and ovariectomized/estrogen-treated rats to compare neurons of these areas to other neurons (specifically the ventrolateral thalamus), and to determine the effects of estrogen on these cells. The neurons of the VMN contain a large nucleus with a prominent nucleolus, rough endoplasmic reticulum (RER), polysomes, a Golgi complex, coated, uncoated and dense-cored vesicles, lysosome-like bodies, inclusion bodies, multivesicular bodies, whorl bodies and myelin figures. Similar organelles were present in the neurons of the ventrolateral thalamus, although polysomes were more prominent, and the cells lacked dense-cored vesicles in the perikarya. Differences in the cells of the VMN between ovariectomized/control and ovariectomized/estrogen-treated rats included a more conspicuous stacking of the RER and greater number of dense-cored vesicles in the estrogen-treated group in both the ventrolateral and dorsomedial subdivisions. In both areas the differences were statistically significant, although more marked in the ventrolateral subdivision. In both VMN subdivisions, the increased stacking of the RER could be correlated with the greater number of dense-cored vesicles and may reflect increased biosynthesis of a secretory product.Supported by grants from the National Institutes of Health (1 R01 NS15889-01) to R.S.C. and (HD-05751) to D.W.P.     

Voluntary exercise contributed to an amelioration of abnormal feeding behavior,locomotor activity and ghrelin production concomitantly with a weight reduction in high fat diet-induced obese rats

In the present study, effects of voluntary exercise in an obese animal model were investigated in relation to the rhythm of daily activity and ghrelin production. Male Sprague–Dawley rats were fed either a high fat diet (HFD) or a chow diet (CD) from four to 16 weeks old. They were further subdivided into either an exercise group (HFD-Ex, CD-Ex) with a running wheel for three days of every other week or sedentary group (HFD-Se, CD-Se). At 16 weeks old, marked increases in body weight and visceral fat were observed in the HFD-Se group, together with disrupted rhythms of feeding and locomotor activity. The induction of voluntary exercise brought about an effective reduction of weight and fat, and ameliorated abnormal rhythms of activity and feeding in the HFD-Ex rats. Wheel counts as voluntary exercise was greater in HFD-Ex rats than those in CD-Ex rats. The HFD-obese had exhibited a deterioration of ghrelin production, which was restored by the induction of voluntary exercise. These findings demonstrated that abnormal rhythms of feeding and locomotor activity in HFD-obese rats were restored by infrequent voluntary exercise with a concomitant amelioration of the ghrelin production and weight reduction. Because ghrelin is related to food anticipatory activity, it is plausible that ghrelin participates in the circadian rhythm of daily activity including eating behavior. A beneficial effect of voluntary exercise has now been confirmed in terms of the amelioration of the daily rhythms in eating behavior and physical activity in an animal model of obesity.     

Study of electrical activity in the area of the hypothalamic ventromedial nucleus and the lateral hypothalamus of rats fed on a high protein and high fat diet.

The authors studied bioelectric potentials in the area of the hypothalamic ventromedial nucleus and the lateral hypothalamus of rats fed on a standard, a high protein and a high fat diet. On the first 3--6 days after changing from the standard to the high fat and high protein diets, a decrease in the amplitude of electrical activity was recorded in both the areas in question. It was also found that the frequency of electrical activity in the hypothalamic ventromedial nucleus or the lateral hypothalamus rose, after 3 days administration of the high fat or the high protein diet, in correlation to the type of diet, and that, in the frequency spectrum, a change occurred in the proportion of basic frequency in relation to superimposed frequencies distorting it. It was further found that there was a permanent difference between the amplitude of electrical activity in the lateral hypothalamus and the hypothalamic ventromedial nucleus.     

Effects of reserpine on dopamine metabolite in the nucleus accumbens and locomotor activity in freely moving rats

The effect of reserpine (2 mg/kg i.p.) on both locomotor activity and the turnover of dopamine metabolite in the rat nucleus accumbens was estimated by using an activity monitor (Animex) and by in vivo brain microdialysis. Three to five hours after reserpine administration locomotor activity was reduced and there was a concomitant increase in the level of the dopamine metabolite, homovamillic acid. These findings suggest that depletion of dopamine from the nucleus accumbens may result in decreased locomotor activity. The data support the notion that dopamine in this tissue contributes to the control of locomotion.     

Effect of ghrelin on chronic liver injury and fibrogenesis in male rats: Possible role of nitric oxide

Recent studies have revealed that ghrelin may be an antioxidant and anti-inflammatory agent in many organs, however its role in chronic liver injury (CLI) remains unclear. The role of nitric oxide (NO) in CLI is controversial as evidence suggests that NO is either a primary mediator of liver cell injury or exhibits a protective effect against injurious stimuli. Recent evidence demonstrated that the therapeutic potential for ghrelin was through eNOS activation and increase in NO production. However, its role on NO production in the liver has not been previously investigated. The aim of this study was to investigate the role of ghrelin in treatment of CLI, and whether this action is mediated through NO. Forty male rats were divided into four groups: Group I: Control; Group II: chronic liver injury (CLI); Group III: CLI + Ghrelin; and Group IV: CLI + Ghrelin + l-NAME. Liver enzymes and tumor necrosis factor alpha (TNF-α), were measured to assess hepatocellular injury. Liver tissue collagen content, malondialdehyde (MDA), gene expression of Bax, Bcl-2, and eNOS were assessed to determine the mechanism of ghrelin action. Results showed that ghrelin decreased serum liver enzymes and TNF-α levels. Ghrelin also reduced liver tissue collagen, MDA, and Bax gene expression, and increased Bcl-2 and eNOS gene expression. The effects on TNF-α, collagen, MDA, Bax, and eNOS were partially reversed in Group IV, suggesting that ghrelin's action could be through modulation of NO levels. Therefore, ghrelin's hepatoprotective effect is partially mediated by NO release.     

Effects of stimulating the central gray matter on neuronal activity in the trigeminal nucleus

A comparative study was conducted on the effects of stimulating different central gray matter (CGM) areas on neuronal activity of the trigeminal nucleus during nociceptive stimulation before and after complete section of medial brainstem structures. The possible role of opiate and non-opiate systems in inhibition of nocieptive afferents is discussed. The CGM was found to be a functionally diverse structure: pain-suppressing and pain-promoting systems exist side by side at this site. The inhibitory influence of the ventromedial CGM is exerted by activation of raphe nucleus neurons; that of the dorsomedial area could well be mediated by involvement of the lateral bulbar area and/or activation of rostral brain structures.I. S. Bertiashvili Institute of Physiology, Academy of Sciences of the Georgian SSR. Tbilisi. Translated from Neirofiziologiya, Vol. 22, No. 3, pp. 381–387, May–June, 1990.     

Effects of second generation tetracyclines on penicillin-epilepsy-induced hippocampal neuronal loss and motor incoordination in rats

Epileptic seizures cause pathological changes such as sclerosis and pyramidal neuronal loss in the hippocampus. Experimentally, epilepsy can be induced by application of various chemicals directly to the cerebral cortex. In this study, epilepsy was induced in rats by intracortical application of 500 IU penicillin G, and the effect of minocycline and doxycycline on the resulting motor incoordination (rotarod) and hippocampal neuronal loss in CA1, CA2 and CA3 fields (optical fractionator method) were investigated. The rotarod performance was reduced in the epilepsy group to 285.1+/-6.9 s (P<0.05 vs. sham-300 s). Minocycline and doxycycline increased this performance to 297.4+/-1.0 s and 296.9+/-1.2 s respectively. No significant difference was detected between minocycline and doxycycline. The present results also showed that the number of neurons (x10(3)) in the sham group was 150+/-9. In the penicillin-epileptic rats, the number was decreased to 105+/-7 (P<0.01). Minocycline, but not doxycycline (125+/-8), significantly increased the number to 131+/-3 (P<0.05). In conclusion, the second generation tetracycline minocycline decreased the loss of hippocampal neurons and motor incoordination in penicillin-epileptic rats. Minocycline could protect against a variety of neurological insults including epilepsy.     

The role of C-terminal part of ghrelin in pharmacokinetic profile and biological activity in rats

Ghrelin is an endogenous ligand for growth hormone secretagogue receptor 1a (GHS-R1a), and consists of 28 amino acid residues with octanoyl modification at Ser³. The previous studies have revealed that N-terminal part of ghrelin including modified Ser³ is the active core for the activation of GHS-R1a. On the other hand, the role of C-terminal (8-28) region in ghrelin has not been clarified yet. In the present study, we prepared human ghrelin, C-terminal truncated ghrelin derivatives and anamorelin, a small molecular GHS compound which supposedly mimics the N-terminal active core, and examined GHS-R1a agonist activity in vitro, pharmacokinetic (PK) profile and growth hormone (GH) releasing activity in rats. All compounds demonstrated potent GHS-R1a agonist activities in vitro. Although the lack of C-terminal two amino acids did not modify PK profile and GH releasing activity, the deletion of C-terminal 8 and 20 amino acids affected them, and ghrelin(1-7)-Lys-NH₂ exhibited very short plasma half-life and low GH releasing activity in vivo. In rat plasma, ghrelin(1-7)-Lys-NH₂ was degraded more rapidly than ghrelin, suggesting that C-terminal part of ghrelin protected octanoylation of Ser³ from plasma esterases. Subdiaphragmatic vagotomy significantly attenuated GH response to ghrelin but not to anamorelin. These results suggest that the C-terminal part of ghrelin has an important role in the biological activity in vivo. We also found that ghrelin stimulated GH release mainly via a vagal nerve pathway but anamorelin augmented GH release possibly by directly acting on brain in rats.     

Modifications of neuronal activity in the rat hypothalamic supraoptic nucleus after long-lasting vibrational stimulation

We analyzed the background impulse activity (BIA) generated by neurons of the rat hypothalamic supraoptic nucleus in the norm and under conditions of long-lasting vibrational stimulation (exposure 5, 10, or 15 days). Distributions of neurons by the level of regularity, dynamics of discharge trains, form of histograms of interspike intervals (ISIs), as well as distributions of neurons by the BIA frequency ranges, were studied. We also calculated the mean frequency of impulsation of the neurons under study and the coefficient of variation of ISIs. After vibrational influences, we found modifications of both the internal structure of the recorded spike trains and the mean frequency of impulsation within the entire studied group and different frequency subgroups. Neirofiziologiya/Neurophysiology, Vol. 38, No. 3, pp. 224–230, May–June, 2006.     

Effects of iptakalim on extracellular glutamate and dopamine levels in the striatum of unilateral 6-hydroxydopamine-lesioned rats: a microdialysis study

In a previous study, we demonstrated that iptakalim (Ipt) significantly ameliorated hypolocomotion and catalepsy induced by haloperidol and rotenone in rats. In order to further understand the mechanism(s), using a rat model of Parkinson's disease (PD) established by unilateral 6-hydroxydopamine (6-OHDA) administration to the substantia nigra pars compacta (SNpc) and reverse microdialysis techniques with high performance liquid chromatography (HPLC), we investigated the effects of Ipt on extracellular levels of glutamate, dopamine (DA) and its metabolite dihydroxyphenylacetic acid (DOPAC) in the striatum of conscious and freely moving rats. The results indicated that unilateral 6-OHDA-lesioned rats have a significantly higher level of extracellular glutamate and a lower level of extracellular DOPAC in the lesioned-side of the striatum, and a lower level of extracellular DA in both sides of the striatum compared to the striatum of control rats. Ipt reduced extracellular glutamate levels in both sides of striatum of the lesioned and control rats in a concentration-dependent manner. Ipt, at lower concentrations (0.01, 0.1, 1 microM), enhanced extracellular DA levels in the lesioned-side striatum of the unilateral 6-OHDA-lesioned rats, while causing no significant changes in the intact side striatum, and even a significant decline in striatum of control rats at higher concentrations of Ipt (10, 100 microM). In addition, Ipt also caused a significant decline in the extracellular DOPAC levels in the lesioned-side striatum of unilateral 6-OHDA-lesioned rats. These data suggest that the major mechanism underlying the ameliorative effects of Ipt on the behavior in 6-OHDA-lesioned rats is the alteration of levels of extracellular neurotransmitters, such as glutamate and DA in the striatum of unilateral 6-OHDA-lesioned rats.     

Effects of high-fat feeding and fasting on ghrelin expression in the mouse stomach

Ghrelin is a peptide identified as an endogenous ligand for the growth hormone secretagogue receptor. Studies have shown that ghrelin stimulates growth hormone, promotes food intake and decreases energy expenditure. Furthermore, feeding status seems to influence plasma ghrelin levels, as these are increased during fasting, whereas feeding and oral glucose intake reduce plasma ghrelin. This study examined whether standardized obesity and fasting affect cellular expression of ghrelin. Specimens from the gastrointestinal tract of fed or 18-h fasted, low-fat or high-fat fed (10 weeks on diet) C57BL/6J mice were studied by immunocytochemistry (ICC) for ghrelin and in situ hybridization (ISH) for ghrelin mRNA. Ghrelin was expressed in especially the corpus but also the antrum of the stomach of all groups studied. Cells positive for ghrelin and ghrelin mRNA in the stomach were reduced in high-fat fed mice. In contrast, ghrelin expression was not affected by fasting. The reduction in ghrelin expression in the high-fat fed mice was associated with a reduction in plasma levels of ghrelin, whereas after fasting, when expression rate was not altered, there was an increase in plasma ghrelin. In conclusion, ghrelin is highly expressed in the corpus and antrum of the stomach of C57BL/6J mice. This expression is reduced in obesity, whereas fasting has no effect.     

The effect of acute alcoholization on the neuronal activity of the normal ventromedial hypothalamus and in pharmacological actions on the brain monoaminergic and opiate systems]

In experiments on white outbred male rats the specificity was studied of the influence and mechanisms of action of acute alcoholization (30%-solution of ethanol, intraperitoneally, 0.7 g/kg) on the activity of functionally different neurones of the ventromedial hypothalamus. Experimental results showed that the neurones, the activity of which lowered after saturation (I-st type), increased the discharges frequency at administration of ethanol. Nerve cells, the activity of which increased (II-nd type) and did not change (III-nd type) after saturation, had inhibitory character of reaction in response to alcoholization. The increase of serotonin content in the brain elicited by intraperitoneal administration of 5-OTPh (50 mg/kg) blockaded the action of ethanol on the nerve cells of the I-st type and did not change the effect of the alcohol on the neurones of the II-nd and III-nd types. Preliminary lowering of the noradrenaline level in the brain (disulphiram, intraperitoneally, 100 mg/kg) and blockade of opiate receptors (nalorphine, 5 mg/kg) fully eliminated ethanol influence on the activity of all types of neurones.