Effects of Maternal Ethanol Consumption and Buspirone Treatment on 5-HT_(1A) and 5-HT_(2A) Receptors in Offspring

Kim, Jung-Ae,Gilespie, Roberta A.,Druse, Mary J. 영남대학교 약품개발연구소 1998 영남대학교 약품개발연구소 연구업적집 Vol.8 No.-

In utero ethanol exposure results in a decreased concentration of serotonin (5-HT) in brain regions containing the cell bodies of 5-HT neurons and their cortical projections. The concentration of 5-HT reuptake sites is also reduced in several brain areas. The present study extended prior work by evaluating the effects of chronic maternal ethanol consumption and maternal buspirone treatment on 5-HT_(1A) and 5-HT_(2A) receptors in mutiple brain areas of offspring. Receptors were quantitated early in postnatal development and at an age when the 5-HT networks are normally well-established. Because fetal 5-HT functions as an essential neurotrophic factor, these studies also determined whether treatment of pregnant rats with buspirone, a 5-HT_(1A) agonist, could overcome the effects of the fetal 5-HT deficit and prevent ethanol-associated receptor abnormalities. The results demonstrated that in utero ethanol exposure significantly alters the binding of 0.1 nM [³H]-8-hydroxy-dipropylaminotetralin to 5-HT_(1A) receptors in developing animals. Ethanol impaired the development of 5-HT_(1A) receptors in the frontal cortex, parietal cortex, and lateral septum; these receptors did not undergo the normal developmental increase between postnatal days 19 and 35. The dentate gyrus was also sensitive to the effects of in utero ethanol exposure. 5-HT_(1A) receptors were increased in this region at 19 days. Maternal buspirone treatment prevented the ethanol-associated abnormalities in 5-HT_(1A) receptors in the dentate gyrus, frontal cortex, and lateral septum. Neither maternal ethanol consumption nor buspirone treatment altered the binding of 2 nM [³H]ketanserin to 5-HT_(2A) receptors in the ventral dentate gyrus,dorsal raphe, parietal and frontal cortexes, striatum, substantis nigra, or nucleus accumbens.

Nelumbinis Semen Reverses a Decrease in 5-HT_(1A) Receptor Binding Induced by Chronic Mild Stress, a Depression-like Symptom

Jang, Choon-Gon,Kang, Moonkyu,Cho, Jae-Han,Lee, Sun-Bok,Kim, Hyuntaek,Park, Soonkwon,Lee, Jinwoo,Park, Seong-Kyu,Hong, Moochang,Shin, Min Kyu,Shim, In-Sup,Bae, Hyunsu WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2004 東西醫學硏究所 論文集 Vol.2004 No.-

Depression is associated with a dysfunctional serotonin (5-hydroxytryptamine; 5-HT) system. More recently, several lines of evidence suggest that an important factor in the development of depression may be a deficit in the function and expression of 5-HT_(1A) receptors. The present study assessed if Nelumbinis Semen (N. s.) had an anti-depression effect through reversing a decrease in 5-HT_(1A) receptor binding in rats with depression-like symptoms induced by chronic mild stress. Using a 5-HT_(1A) receptor binding assay, with a specific 5-HT_(1A) receptor agonist, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin), the mechanism of the anti-depression effect of N. s. on rats was investigated, and the effects compared with two well-known antidepressants, Hyperium Perforatum (St. Johns Wort) and fluoxetine (Prozac). Animals were divided into live groups: the normal (N) group without chronic mild stress (CMS), the control (C) group under CMS for 8 weeks, the Nelumbinis Semen (N. s.) treatment group under CMS for 8 weeks, the Hyperium Perforatum (H. p.) treatment group under CMS for 8 weeks and finally, the fluoxetine (F) treatment group under CMS for 8 weeks. Each treatment was administered to rats during the last 4 weeks of the 8-week CMS. A sucrose intake test was performed to test the anti-depression effect of N. s. The N. s. treatment significantly reversed the decreased sucrose intake under CMS (P<0.05 compared to control group under CMS). In the CA2 and CA3 regions of the hippocampus, both N. s. and H. p. reversed the CMS-induced decrease in 5-HT_(1A) receptor binding. In the Ⅰ to II regions of the frontal cortex, N. s. and H. p. also reversed the CMS-induced decrease in 5-HT_(1A) receptor binding, and even showed a significant increase in 5-HT_(1A) receptor binding compared to the F treatment group (N. s. vs. P₁ p<0.05, H. p. vs. P₁ p<0.05). However, in the hypothalamus, all treatments reversed the CMS-induced decrease in 5-HT_(1A) receptor binding. This reversal effect of N. s. on the decrease in 5-HT_(1A) receptor binding in the frontal cortex, hippocampus and hypothalamus of rat brains was very similar to that of H. p, but different from that of F. It is concluded that N. s. presents an anti-depression effect through enhancing 5-HT_(1A) receptor binding.

Nelumbinis Semen Reverses a Decrease in $5-HT_{1A}$Receptor Binding Induced by Chronic Mild Stress, a Depression-like Symptom

Jang, Choon-Gon,Kang, Moon-Kyu,Cho, Jae-Han,Lee, Sun-Bok,Kim, Hyun-Taek,Park, Soon-Kwon,Lee, Jin-Woo,Park, Seong-Kyu,Hong, Moo-Chang,Shin, Min-Kyu,Shim, In-Sup,Bae , Hyun-Su The Pharmaceutical Society of Korea 2004 Archives of Pharmacal Research Vol.27 No.10

Depression is associated with a dysfunctional serotonin (5-hydroxytryptamine; 5-HT) system. More recently, several lines of evidence suggest that an important factor in the development of depression may be a deficit in the function and expression of $5-HT_{1A}$ receptors. The present study assessed if Nelumbinis Semen (N. s.) had an anti-depression effect through reversing a decrease in $5-HT_{1A}$receptor binding in rats with depression-like symptoms induced by chronic mild stress. Using a $5-HT_{1A}$ receptor binding assay, with a specific $5-HT_{1A}$receptor agonist, 8- OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin), the mechanism of the anti-depression effect of N. s. on rats was investigated, and the effects compared with two well-known antidepressants, Hyperium Perforatum (St. Johns Wort) and fluoxetine (Prozac). Animals were divided into five groups: the normal (N) group without chronic mild stress (CMS), the control (C) group under CMS for 8 weeks, the Nelumbinis Semen (N. s.) treatment group under CMS for 8 weeks, the Hyperium Perforatum (H. p.) treatment group under CMS for 8 weeks and finally, the fluoxetine (F) treatment group under CMS for 8 weeks. Each treatment was administered to rats during the last 4 weeks of the 8-week CMS. A sucrose intake test was performed to test the anti-depression effect of N. s. The N. s. treatment significantly reversed the decreased sucrose intake under CMS (P<0.05 compared to control group under CMS). In the CA2 and CA3 regions of the hippocampus, both N. s. and H. p. reversed the CMS-induced decrease in $5-HT_{1A}$receptor binding. In the I to II regions of the frontal cortex, N. s. and H. p. also reversed the CMS-induced decrease in$5-HT_{1A}$receptor binding, and even showed a significant increase in $5-HT_{1A}$receptor binding compared to the F treatment group (N. s. vs. P, p<0.05, H. p. vs. P, p<0.05). However, in the hypothalamus, all treatments reversed the CMSinduced decrease in $5-HT_{1A}$receptor binding. This reversal effect of N. s. on the decrease in $5-HT_{1A}$receptor binding in the frontal cortex, hippocampus and hypothalamus of rat brains was very similar to that of H. p, but different from that of F. It is concluded that N. s. presents an anti-depression effect through enhancing $5-HT_{1A}$receptor binding.

Nelumbinis Semen Reverses a Decrease in 5-HT1A Receptor Binding Induced by Chronic Mild Stress, a Depression-like Symptom

장춘곤,강문규,Jae-Han Cho,Sun-Bok Lee,Hyuntaek Kim,박순권,Jinwoo Lee,박성규,Moochang Hong,Min Kyu Shin,심인섭,배현수 대한약학회 2004 Archives of Pharmacal Research Vol.27 No.10

Depression is associated with a dysfunctional serotonin (5-hydroxytryptamine; 5-HT) system. More recently, several lines of evidence suggest that an important factor in the development of depression may be a deficit in the function and expression of $5-HT_{1A}$ receptors. The present study assessed if Nelumbinis Semen (N. s.) had an anti-depression effect through reversing a decrease in $5-HT_{1A}$receptor binding in rats with depression-like symptoms induced by chronic mild stress. Using a $5-HT_{1A}$ receptor binding assay, with a specific $5-HT_{1A}$receptor agonist, 8- OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin), the mechanism of the anti-depression effect of N. s. on rats was investigated, and the effects compared with two well-known antidepressants, Hyperium Perforatum (St. Johns Wort) and fluoxetine (Prozac). Animals were divided into five groups: the normal (N) group without chronic mild stress (CMS), the control (C) group under CMS for 8 weeks, the Nelumbinis Semen (N. s.) treatment group under CMS for 8 weeks, the Hyperium Perforatum (H. p.) treatment group under CMS for 8 weeks and finally, the fluoxetine (F) treatment group under CMS for 8 weeks. Each treatment was administered to rats during the last 4 weeks of the 8-week CMS. A sucrose intake test was performed to test the anti-depression effect of N. s. The N. s. treatment significantly reversed the decreased sucrose intake under CMS (P<0.05 compared to control group under CMS). In the CA2 and CA3 regions of the hippocampus, both N. s. and H. p. reversed the CMS-induced decrease in $5-HT_{1A}$receptor binding. In the I to II regions of the frontal cortex, N. s. and H. p. also reversed the CMS-induced decrease in$5-HT_{1A}$receptor binding, and even showed a significant increase in $5-HT_{1A}$receptor binding compared to the F treatment group (N. s. vs. P, p<0.05, H. p. vs. P, p<0.05). However, in the hypothalamus, all treatments reversed the CMSinduced decrease in $5-HT_{1A}$receptor binding. This reversal effect of N. s. on the decrease in $5-HT_{1A}$receptor binding in the frontal cortex, hippocampus and hypothalamus of rat brains was very similar to that of H. p, but different from that of F. It is concluded that N. s. presents an anti-depression effect through enhancing $5-HT_{1A}$receptor binding.

5-HT_1A receptor agonist 8-OH-DPAT induces serotonergic behaviors in mice via interaction between PKCδ and p47phox

Tran, Hai-Quyen,Shin, Eun-Joo,Hoai Nguyen, Bao-Chau,Phan, Dieu-Hien,Kang, Min-Ji,Jang, Choon-Gon,Jeong, Ji Hoon,Nah, Seung-Yeol,Mouri, Akihiro,Saito, Kuniaki,Nabeshima, Toshitaka,Kim, Hyoung-Chun Elsevier 2019 Food and chemical toxicology Vol.123 No.-

<P><B>Abstract</B></P> <P>Serotonin syndrome is an adverse reaction due to increased serotonin (5-hydroxytryptophan: 5-HT) concentrations in the central nervous system (CNS). The full 5-HT<SUB>1A</SUB> receptor (5-HT<SUB>1A</SUB>R) agonist (±)-8-hydroxy-dipropylaminotetralin (8-OH-DPAT) has been recognized to elicit traditional serotonergic behaviors. Treatment with 8-OH-DPAT selectively increased PKCδ expression out of PKC isoforms and 5-HT turnover rate in the hypothalamus of wild-type mice. Treatment with 8-OH-DPAT resulted in oxidative burdens, co-immunoprecipitation of 5-HT<SUB>1A</SUB>R and PKCδ, and phosphorylation and membrane translocation of p47phox. Importantly, p47phox also interacted with 5-HT<SUB>1A</SUB>R or PKCδ in the presence of 8-OH-DPAT. Consistently, the interaction and oxidative burdens were attenuated by 5-HT<SUB>1A</SUB>R antagonism (i.e., WAY100635), PKCδ inhibition (i.e., rottlerin and genetic depletion of PKCδ), or NADPH oxidase/p47phox inhibition (i.e., apocynin and genetic depletion of p47phox). However, WAY100635, apocynin, or rottlerin did not exhibit any additive effects against the protective effect by inhibition of PKCδ or p47phox. Furthermore, apocynin, rottlerin, or WAY100635 also significantly protected from pro-inflammatory/pro-apoptotic changes induced by 8-OH-DPAT. Therefore, we suggest that 8-OH-DPAT-induced serotonergic behaviors requires oxidative stress, pro-inflammatory, and pro-apoptotic changes, that PKCδ or p47phox mediates the serotonergic behaviors induced by 8-OH-DPAT, and that the inhibition of PKCδ-dependent p47phox activation is critical for protecting against serotonergic behaviors.</P> <P><B>Highlights</B></P> <P> <UL> <LI> 8-OH-DPAT significantly increases PKCδ expression and 5-HT turnover rate in the hypothalamus of mice. </LI> <LI> 8-OH-DPAT induces oxidative burdens and interactions of “5-HT<SUB>1A</SUB>R and PKCδ”, “5-HT<SUB>1A</SUB>R and PKCδ”, and “PKCδ and p47phox”. </LI> <LI> Oxidative, inflammatory, apoptotic changes by 8-OH-DPAT are attenuated via inhibition of 5-HT<SUB>1A</SUB>R, PKCδ, or PHOX/p47phox. </LI> <LI> PKCδ or p47phox mediates the increase in 5-HT turnover rate and serotonergic behaviors induced by 8-OH-DPAT. </LI> <LI> The inhibition of PKCδ-dependent p47phox activation is critical for attenuating against the serotonergic behaviors. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Effects of 5HT1A Activation on Depression Profile Following 5-HT Depletion in Rats Lacking Social Attachment Since Weanling

Kuo-Jung Chang,Yu-Jung Chen,Jing-Yi Chung,Chen-Cheng Lin,Yia-Ping Liu 대한신경정신의학회 2018 PSYCHIATRY INVESTIGATION Vol.15 No.11

Objective Post weanling isolation-reared (IR) rats are featured with depressive phenotype, yet its mechanism is not clearly defined particularly in terms of the involvement of central 5-HT1A receptors. The present study aims to examine the effects of 5HT1A activation on forced swim test (FST) in IR rats following 5-HT depletion. Methods Social control (SOC) and IR rats received an intracerebraoventricular (ICV) injection of 5-HT depletion agent, 5,7-DHT. 14 days after the surgery, rats were assessed their performance in FST with or without the challenge with a 5-HT1A agonist, 8-OH-DPAT. Rats were then sacrificed for analyzing their 5-HT tissue levels and the expressions of their 5-HA1A receptors in prefrontal cortex (PFC), hippocampus (HPX), and amygdala (AMY). Results 5,7-DHT decreased the tissue concentration of 5-HT in both IR and SOC rats. IR rats were more immobile and less sensitive to the lesion-induced immobility, however this effect was reversed by acute challenge of 8-OH-DPAT. 5,7-DHT lesion increased the expression of PFC 5-HT1A receptors. Conclusion The integrity of central 5-HT system is developmentally crucial for the 5-HT1A-relevant depression profile in rats of social isolation.

중추내로 투여한 5-HT<SUB>1A</SUB> 작동제에 의한 마취 가토에 있어서 신장기능의 변동

임영채(Young Chai Lim),김경심(Kyung Shim Kim),국영종(Young Johng Kook),고정태(Jeong Tae Koh) 대한생리학회-대한약리학회 1997 The Korean Journal of Physiology & Pharmacology Vol.1 No.3

<P> Central tryptaminergic system has been shown to play an important role in the regulation of renal function: 5-HT<SUB>1</SUB>(5-hydroxytryptamine<SUB>1</SUB>) receptors might seem to mediate the diuresis and natriuresis, whereas the 5-HT<SUB>2</SUB> and 5-HT<SUB>3</SUB> receptors mediate the antidiuretic and antinatriuretic effects. This study attempted to delineate the role of central 5-HT<SUB>1A</SUB> subtype in the regulation of rabbit renal function by observing the renal effects of intracerebroventricularly(icv)-administered PAPP(p-aminophenylethyl-m-trifluoromethylphenyl piperazine, LY165163), a selective agonist of 5-HT<SUB>1A</SUB> receptors. PAPP in doses ranging from 40 to 350 ㄍg/kg icv induced significantly diuresis, natriuresis, and kaliuresis, along with increased renal perfusion and glomerular filtration. Systemic blood pressure was also increased. Free water reabsorption(T<SUP>c</SUP>H<SUB>2</SUB>O), a measure of ADH(antidiuretic hormone) secretion, was increased also. Intravenous 350 ㄍg/kg of PAPP elicited antidiuresis and antinatriuresis together with decreased blood pressure, thus indicating that the effects of icv PAPP were brought about through the central mechanisms, not by direct peripheral effects of the drug on kidney. Ketanserin, a selective 5-HT<SUB>2</SUB> antagonist, 40 ㄍg/kg icv, did not affect the renal effects of the icv PAPP. Methysergide, a non-selective 5-HT<SUB>1</SUB> antagonist, also did not block the renal functional responses by the icv PAPP. NAN-190, a 5-HT<SUB>1A</SUB> antagonist, also did not antagonized the renal action of the icv PAPP. However the increased free water reabsorption was abolished by both methysergide or ketanserin pretreatment. The increments of blood pressure by icv PAPP was blocked only by NAN-190 pretreatment. These observations suggest that the central 5-HT<SUB>1A</SUB> receptor might be involved in the central regulation of rabbit renal function by exerting the diuretic and natriuretic influences.

생애초기 저산소증으로 인한 신경행동기형

이성수,이서울,강동원,김진수,김동구 대한신경과학회 1998 대한신경과학회지 Vol.16 No.2

Effects of 5HT1A Activation on Depression Profile Following 5-HT Depletion in Rats Lacking Social Attachment Since Weanling

Kuo-Jung Chang,Yu-Jung Chen,Jing-Yi Chung,Chen-Cheng Lin,Yia-Ping Liu 대한신경정신의학회 2018 PSYCHIATRY INVESTIGATION Vol.15 No.10

Objective: Post weanling isolation-reared (IR) rats are featured with depressive phenotype, yet its mechanism is not clearly defined particularly in terms of the involvement of central 5-HT1A receptors. The present study aims to examine the effects of 5HT1A activation on forced swim test (FST) in IR rats following 5-HT depletion. Methods: Social control (SOC) and IR rats received an intracerebraoventricular (ICV) injection of 5-HT depletion agent, 5,7-DHT. 14days after the surgery, rats were assessed their performance in FST with or without the challenge with a 5-HT1A agonist, 8-OH-DPAT. Rats were then sacrificed for analyzing their 5-HT tissue levels and the expressions of their 5-HA1A receptors in prefrontal cortex (PFC), hippocampus (HPX), and amygdala (AMY). Results: 5,7-DHT decreased the tissue concentration of 5-HT in both IR and SOC rats. IR rats were more immobile and less sensitive to the lesion-induced immobility, however this effect was reversed by acute challenge of 8-OH-DPAT. 5,7-DHT lesion increased the expression of PFC 5-HT1A receptors. Conclusion: The integrity of central 5-HT system is developmentally crucial for the 5-HT1A-relevant depression profile in rats of social isolation.

Buspirone-induced Prolactin Secretion in Man is Not $5-HT_{1A}$ Receptor Mediated: Effect of Pindolol Pretreatment

Lee, Hong-Shick,Nash, J. Frank,Meltzer, Herbert Y. The Korean Society of Pharmacology 1992 대한약리학잡지 Vol.28 No.1

Nonbenzodiazepine계 항불안제인 buspirone을 이용하여 건강한 8명의 남자를 대상으로 prolactin과 cortisol분비를 측정하였다. Buspirone는 $Dopamine_2$ 수용체 antagonist 성질 뿐 아니라 $5-HT_{1A}$ partial agonist 효과가 있는 것으로 보고되고 있다. Buspirone 30mg 경구투여시 혈청 prolactin 농도는 유의한 증가를 보였으나 혈청 cortisol 농도의 변화는 차이가 없었다. beta adrenoreceptor antagonist이면서 $5-HT_{1A}$ 수용체 antagonist로 알려진 pindolol (30mg)을 경구 투여한 결과 기초 혈청 prolactin이나 cortisol 농도는 유의한 차이가 없었다. Pinodlol을 전처치한 경우 buspirone-induced prolaction 분비의 유의한 억제효과는 없었다. 이상의 성적은 buspirone-induced prolactin 분비증가는 아마도 $5-HT_{1A}$ 수용체 활성과 관련되지 않음을 시사하는 것으로 사료된다. The effect of the nonbenzodiazepine anxiolytic, buspirone $(Buspar^R)$, a serotonin $(5-HT)_{1A}$ partial agonist, which also has dopamine $(DA)_2$ receptor antagonist properties, on prolactin and cortisol secretion was examined in eight normal male volunteers. The oral administration of buspirone (30 mg) significantly increased plasma prolactin concentrations but did not significantly increase plasma cortisol concentrations in this study. The oral administration of pindolol (30 mg), a beta adrenoceptor antagonist which is also a $5-HT_{1A}$ receptor antagonist, had no significant effect on basal prolactin or cortisol levels. Moreover, pretreatment with pindolol did not significantly inhibit the buspirone-induced increase in prolactin secretion. These preliminary data are suggestive that buspirone-induced prolactin secretion is not mediated via $5-HT_{1A}$ receptor activation.