Cholecystokinin Excites Neostriatal Neurons in Rats via CCKA or CCKB Receptors

The effect of iontophoretically applied cholecystokinin (CCK) on neurons of the neostriatum was studied in rats anaesthetized with urethane. The most frequently observed effect of the sulphated octapeptide (CCK-8S) on striatal neurons was excitation. Spontaneously active neurons responded more often to CCK-8S than quiescent cells. Silent, primarily non-responsive neurons could often be stimulated with CCK-8S using glutamate to induce an ongoing discharge. Thus, 45.8% of the 177 neurons studied changed their discharge rate by more than 30%. Certain CCK receptor antagonists could prevent the effect of CCK-8S, fully or at least partly, in the majority of CCK-responsive neurons. The data suggest that cholecystokinin modulates the firing of active neostriatal neurons via the CCKA or the CCKB receptor type. Furthermore, we compared neuronal responses to glutamate with those recorded during concomitant administration of CCK-8S in order to study the interaction of both transmitters, which may be colocalized in striatal afferents. CCK-8S mainly enhanced the excitatory effect of glutamate on striatal neurons, but in several neurons the response to glutamate was reduced. The CCKB receptor antagonist could prevent CCK-8S from increasing the glutamate-induced activation.     

Baclofen Pretreatment Attenuates the Suppressant Effect of Intraperitoneal Administration of Cholecystokinin (CCK) on Food Intake in Rats

The aim of this study was to investigate whether pretreatment with the GABAB receptor agonist baclofen could prevent the inhibitory effect of systemically administered cholecystokinin (CCK) on food intake in rats. Baclofen (2 mg/kg, SC) administered 60 min prior to IP injection of CCK (5 μg/kg) significantly attenuated the suppressant effect of the peptide on feeding in nondeprived rats (Experiment 1) and rats that had been deprived of food for 22 h (Experiment 2). Baclofen had no significant effects on food intake when administered alone. The results suggest that the inhibitory effect of exogenous peripheral CCK on food intake may be dependent on an interaction with a GABAB-receptor mediated mechanism. Copyright © 1996 Elsevier Science Inc.     

Chronic neuroleptic-induced mouth movements in the rat: suppression by CCK and selective dopamine D1 and D2 receptor antagonists

Fluphenazine decanoate (25 mg/kg IM every 3 weeks x 6) resulted in spontaneous vacuous chewing mouth movements and jaw tremor in male Sprague-Dawley rats. These movements could be suppressed by the selective D1 or D2 dopamine antagonists SCH 23390 (0.5 mg/kg) and raclopride (0.5 mg/kg), respectively, and by CCK-8S (50 g/kg). Fluphenazine-induced mouth movements were unaffected by the selective CCK antagonist MK-329, and by a dose of physostigmine (50 g/kg) sufficient to stimulate mouth movements in placebo treated rats. Scopolamine (0.1 mg/kg) suppressed spontaneous mouth movements in placebo-treated rats, but the effect on fluphenazine-induced mouth movements was not significant. A higher dose of scopolamine (0.5 mg/kg) did suppress the neuroleptic-induced mouth movements, but also induced hyperactivity, characterized by increased sniffing and grooming. These findings indicate that mouth movements resulting from the chronic administration of neuroleptics to the rat may serve as a useful pharmacological model of tardive dyskinesia in the human, and suggest that a relative increase of D1 activity as well as impaired CCK function may contribute to the pathogenesis of this disorder.     

Gastric capacity, test meal intake, and appetitive hormones in binge eating disorder

Binge eating disorder (BED), characterized by ingestion of very large meals without purging afterwards, is found in a subset of obese individuals. We showed previously that stomach capacity is greater in obese than in lean subjects, and in this study, we investigated capacity in obese individuals with BED. We also determined ad-libitum intake of a test meal until extremely full. Furthermore, we measured various appetitive hormones (insulin, leptin, glucagon, CCK, ghrelin) and glucose before a fixed meal and for 120 min afterwards. An acetaminophen tracer was used to assess gastric emptying rate. We compared three groups of overweight women: 11 BED, 13 BE (subthreshold BED), and 13 non-binge-eating normals. The BED individuals had the largest stomach capacity as assessed by either maximum volume tolerated (P=.05) or by gastric compliance to pressure (P=.02) using an intragastric balloon. Although test meal intake did not differ between groups, it correlated (P=.03) with gastric capacity. The BED group showed a tendency (P=.06) to have greater area under the curve (AUC) and had higher values at 5 and 60 min (P<.05) for insulin compared to normals. Moreover, the BED subjects had lower ghrelin baselines premeal, and lower AUC for ghrelin, which then declined less postmeal than for the normals (P<.05). None of the other blood values differed, including glucose, leptin glucagon, and CCK, as well as acetaminophen, reflecting gastric emptying. The lower ghrelin in BED, although contrary to what was expected, is consistent with lower ghrelin in obesity, and suggests down-regulation of ghrelin by overeating. The lack of differences in CCK is consistent with the lack of differences in gastric emptying rate, given that CCK is released when nutrients reach the intestine. The results show that BED subjects have a large gastric capacity as well as abnormalities in meal-related ghrelin and insulin patterns that may be factors in binge eating.     

Coexistence of somatostatin- and avian pancreatic polypeptide (APP)-like immunoreactivity in some forebrain neurons

The indirect immunofluorescence technique was used to demonstrate the coexistence of somatostatin together with avian pancreatic polypeptide-like immunoreactivity within certain neurons of the rat forebrain. Numerous neurons containing these peptides were observed in the neocortex, hippocampus, olfactory tubercle, striatum, nucleus accumbens and lateral septum. In studies of serial sections stained alternately for these two peptides, and in restaining experiments, It could be determined that in many neurons in these areas these two peptides coexisted. In other brain areas such as the anterior periventricular hypothalamus, somatostatin cells were never found to contain avian pancreatic polypeptide-like immunoreactivity. Also, within the pancreas these two peptides were never found to coexist in the same cells. The findings represent a further example of the coexistence of more than one neuropeptide within a single neuron.     

Types of nerves in the enteric nervous system

The enteric nervous system is one of the three divisions of the autonomic nervous system, the others being the sympathetic and parasympathetic. In contrast to the other divisions, it can perform many functions independently of the central nervous system. It consists of ganglionated plexuses, their connections with each other, and nerve fibres which arise from the plexuses and supply the muscle, blood vessels and mucosa of the gastrointestinal tract. The enteric nervous system contains a large number of neurons, approximately 10⁷ to 10⁸. About ten or more distinct types of enteric neurons have been distinguished on electrical, pharmacological, histochemical, biochemical and ultrastructural grounds as well as on the basis of their modes of action. Both excitatory and inhibitory nerves supply the muscle and there are inhibitory and excitatory interneurons within the enteric plexuses. There are also enteric nerves which supply intestinal glands and blood vessels, but these receive less emphasis in this commentary.Correlations between groups of neurons defined on different criteria are poor and in many cases the physiological roles of the nerves are not known. The functions of noradrenergic nerves which are of extrinsic origin are reasonably well understood, but cholinergic nerves in the intestine are the only intrinsic nerves for which both the transmitter and to some extent the functions are known. In the case of non-cholinergic, non-noradrenergic enteric inhibitory nerves, the functions are understood but the transmitter is yet to be determined, both adenosine 5′-triphosphate and vasoactive intestinal polypeptide having been proposed. Other nerves have been defined pharmacologically (non-cholinergic excitatory nerves to neurons and muscle, intrinsic inhibitory inputs to neurons, and enteric, non-cholinergic vasodilator nerves) and histochemically (intrinsic amine-handling neurons and separate neurons containing peptides: substance P, somatostatin, enkephalins, vasoactive intestinal polypeptide, gastrin cholecystokinin tetrapeptide, bombesin, neurotensin and probably other peptides). Little is known of the functions of these nerves, although a number of proposals which have been made are discussed.     

Evidence for the involvement of the 5-HT1A receptor in CCK induced satiety in rats

The present study was designed to examine possible interactions between exogenous CCK and the 5-HT_1A receptor subtype mediated serotonergic effects on feeding in rats. The somatodendritic 5-HT_1A receptor agonist 8-OH-DPAT (0.32 mg/kg sc) evoked feeding in freely feeding rats. This effect was attenuated by treatment with CCK-8 (1, 5 and 25 g/kg ip). In food deprived rats, CCK-8 (40 g/kg ip) significantly reduced the size of a test meal. Treatment with the 5-HT_1A receptor antagonist WAY-100135 (10 mg/kg ip) antagonized this anorectic effect of CCK-8. WAY-100135 on its own did not affect food intake. These results suggest the involvement of the 5-HT_1A receptor subtype in mediating 5-HT-CCK interactions in the control of food intake in rats.     

大鼠大脑皮质胆囊收缩素受体的体外结合分析法研究

用Ｂｏｌｔｏｎ－Ｈｕｎｔｅｒ试剂联结法标记胆囊收缩素（ＣＣＫ８）,得１２５Ｉ－ＢＨ－ＣＣＫ８,其比放射性为３．４ＴＢｑ／ｍｍｏｌ,放射化学纯度大于９６％。取其与自制的大鼠大脑皮质细胞膜进行受体放射分析,发现标记配体与大鼠大脑皮质ＣＣＫ受体的结合具有温度和时间依赖性,可饱和性,可逆性及特异性。经Ｓｃａｔｃｈａｒｄ分析获大鼠大脑皮质细胞膜ＣＣＫ受体Ｋｄ值为１．０９８ｎｍｏｌ／Ｌ,Ｂｍａｘ为１９７．５ｆｍｏｌ／ｍｇ蛋白。     

慢性染汞大鼠皮质胆囊收缩素神经元的变化

目的:观察染汞大鼠皮层内CCK阳性神经元的变化与大鼠学习记忆能力之间的关系。方法:选用刚断乳健康Wistar大鼠16只,雄性,由天津市实验动物中心提供。随机分为两组,每组8只,即对照组(饮用单蒸水,普通饲料)、染汞组(饮用4.3 mg/(kg.d)氯化汞水,普通饲料),1月后进行实验。采用Y迷宫方法观察染汞大鼠在学习记忆方面与对照组大鼠的差别。采用CCK抗体免疫组化方法,观察饮用含4.3 mg/(kg.d)氯化汞(HgCl2)饮水的大鼠皮层CCK阳性神经元的变化。结果:染汞大鼠较对照组大鼠学习记忆能力明显降低,差别有显著性;染汞组大鼠皮层CCK阳性神经元的数量较对照组明显减少,差异有显著性。结论:染汞后大鼠皮层CCK阳性神经元表达的减少,可能是汞影响学习记忆的机制之一。     

Inhibitory effects of kratom leaf extract (Mitragyna speciosa Korth.) on the rat gastrointestinal tract

Kratom (Mitragyna speciosa Korth.) is an indigenous plant of Thailand used traditionally in folk medicine although it is claimed to cause addiction. It is used to treat diarrhea, however, there is no scientific evidence to support the use. The aim of this study is to investigate the effect of methanolic extract of kratom leaves on the rat gastrointestinal tract. Kratom extract at 50, 100, 200 and 400 mg/kg (p.o.) caused a dose dependent protection against castor oil-induced diarrhea in rats and also inhibited intestinal transit. The antidiarrheal effect was not antagonized by naloxzone. The inhibition of intestinal transit by kratom extract was significantly different from the control when treated with a single dose for 1 day. For longer-term treatments of 15 and 30 days, kratom extract did not decrease the intestinal transit time indicating that adaptation had occurred. Kratom extract at a dose level of 200 and 400 mg/kg for 30 days and morphine at 3 mg/kg (i.p.) caused a decrease in the increment of body weight that was significantly different from the control and kratom extract at lower doses (50 and 100 mg/kg). However it had no effect on the level of plasma cholecystokinin. The results suggested that methanolic kratom extract exhibited its antidiarrheal effect on rat gastrointestinal tract. The effects may occur via pathways in addition to the action on opioid receptors. High does of kratom extract decreased the increment of body weight similar to the effect of morphine.