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Biphasic firing response of nucleus accumbens neurons elicited by THPB-18 and its correlation with dA receptor subtypes

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Acta Pharmacologica Sinica 2004年第12期25卷 31-39页

作者： Yu FU2,3,4, Zi-tao ZHU2,5, Xing-zu ZHU2, Guo-zhang JIN2,6 2State KeyLaboratory of drug Research,Shanghai Institute ofMateria Medica, Shanghai Institutes for BiologicalSciences, ChineseAcademy of Sciences, Graduate Schoolof the Chinese Academy of Sciences, Shanghai 201203, ChinaNow in department of Pharmacology and Toxicology, Univer-sity of Texas Medical Branch, USA.Now in department of Physiology & Pharmacology, OregonHealth Sciences University, USA,5Now in department of Physiology & Pharmacology, OregonHealth Sciences University, USA, State Key Laboratory of drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 201203 China

AIM: To investigate the possibility whether THPB-18 (l-12-shloroscoulerine) possesses the d1 agonist-d2 antago- nist action on meso-accumbens-mPFC dA system. METHOdS: Single unit spontaneous firing activity was re- corded in the nucleus accumbens (NAc) neurons of na?ve and unilateral-6-hydroxydopamine (6-OHdA)-lesioned Sprague-dawley rats. The effects of drugs applied intravenously or iontophoretically were determined by the change of firing rates. RESULTS: Under normal conditions, the systemic administration of THPB-18 produced a decrease-increase biphasic firing pattern in the NAc neurons during cumulative doses. High dose of THPB-18 was capable of reversing the inhibition induced by both d2 agonist LY171555 and d1/d2 agonist APO on NAc firing activity. Spiperone pretreatment could not block the high dose of THPB-18-induced firing rate increase, which was reversed by the d1 selective antagonist SCH23390. The tested NAc neurons were effectively inhibited by iontophoretically applied THPB-18 in 90 % of 6-OHdA-lesioned rats, while THPB-18 caused variable effects on the firing of NAc neurons in the neurons of unlesioned rats. The inhibitory effect of THPB-18 was blocked by iontophoretic application of SCH23390, but not d2 antagonist spiperone. CONCLUSION: Similar to l-stepholidine, THPB-18 also possesses the “d1 agonistic-d2 antagonistic” dual action on the VTA-NAc dA system.4Now in department of Pharmacology and Toxicology, Univer-sity of Texas Medical Branch, USA.5Now in department of Physiology & Pharmacology, OregonHealth Sciences University, USA,4Now in department of Pharmacology and Toxicology, Univer-sity of Texas Medical Branch, USA.5Now in department of Physiology & Pharmacology, OregonHealth Sciences University, USA,5Now in department of Physiology & Pharmacology, OregonHealth Sciences University, USA,

关键词： berberine dopamine d1 receptors dopamine d2 receptors nucleus accumbens

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Gut-brain crosstalk regulates craving for fatty food

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World Journal of diabetes 2017年第12期8卷 484-488页

作者： Rajendra Raghow department of Veterans Affairs Medical Center department of Pharmacology University of Tennessee Health Science CenterMemphisTN 38163United States

Patients undergoing Roux-en-Y gastric bypass(RYGB)surgery elicit striking loss of body weight. Anatomical restructuring of the gastrointestinal(GI) tract, leading to reduced caloric intake and changes in food preference, are thought to be the primary drivers of weight loss in bariatric surgery patients. However, the mechanisms by which RYGB surgery causes a reduced preference for fatty foods remain elusive. In a recent report, Hankir et al described how RYGB surgery modulated lipid nutrient signals in the intestine of rats to blunt their craving for fatty food. The authors reported that RYGB surgery restored an endogenous fat-satiety signaling pathway, mediated via oleoylethanolamide(OEA), that was greatly blunted in obese animals. In RYGB rats, high fat diet(HFd) led to increased production of OEA that activated the intestinal peroxisome proliferation activator receptors-α(PPARα). In RYGB rats, activation of PPARα by OEA was accompanied by enhanced dopamine neurotransmission in the dorsal striatum and reduced preference for HFd. The authors showed that OEA-mediated signals to the midbrain were transmitted via the vagus nerve. Interfering with either the production of OEA in enterocytes, or blocking of vagal and striatal d1 receptors signals eliminated the decreased craving for fat in RYGB rats. These studies demonstrated that bariatric surgery led to alterations in the reward circuitry of the brain in RYGB rats and reduced their preference for HFd.

关键词： Roux-en-Y gastric bypass surgery dietary lipids dopamine d1 receptors Peroxisome proliferator activated receptor-alpha Oleoylethanolamide

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