Biomedical subjects

K Akiyama

Publications and source records attributed to K Akiyama.

At least 19 recordsLinked to original sources

PubMed1992

Enduring increase in membrane-associated protein kinase C activity in the hippocampal-kindled rat.

In a previous study we demonstrated that the membrane-associated protein kinase C (PKC) activity in the amygdala/pyriform cortex (AM/PC) and both the right and left hippocampus (HIPP) of rats kindled from the left HIPP increased significantly 4 weeks after the occurrence of the last seizure compared with control rats. In this study, we carried out further investigations into the enduring effect of HIPP-kindling on membrane-associated PKC activity, the protein concentrations and brain wet tissue weights of the AM/PC and right (contralateral) and left (ipsilateral) HIPP 15-16 weeks after the last generalized kindled seizure had occurred. In addition, we determined the membrane-associated PKC activity one week after the occurrence of the last partial (stage 1-3) seizure. Fifteen to sixteen weeks after the final kindled full seizure, the membrane-associated PKC activity which was expressed as mol/min per mg protein increased significantly in the AM/PC (by 62%, P < 0.02) and left HIPP (by 33%, P < 0.03) compared with control rats, whereas the cytosolic PKC activities did not differ in any brain region examined. The wet tissue weight increased significantly (by 10%, P < 0.04) in the left HIPP only. Furthermore, when it was expressed as pmol/min per mg wet tissue weight, the membrane-associated PKC activity increased significantly in the AM/PC (by 47%, P < 0.02), right HIPP (by 27%, P < 0.05) and left HIPP (by 35%, P < 0.03) compared with the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Ionotropic excitatory amino acid receptors in discrete brain regions of kindled rats.

A study was performed to examine the specific binding of excitatory amino acid (EAA) receptor subtypes in 5 brain regions of rats kindled from the amygdala or hippocampus, using extensively washed and Triton X-100-treated membranes. Seven days after the last amygdala kindled seizure, [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10- imine maleate ([3H]MK-801) binding, which labels N-methyl-D-aspartate (NMDA)-sensitive receptor-linked cation channels, decreased significantly only in the amygdala of kindled rats compared to that of controls under equilibrium assay conditions. There was no significant change in [3H]MK-801 binding in the amygdala or hippocampus 7 days after the last hippocampal kindled seizure, or 28 days after the last amygdala kindled seizure. Nor was there a significant change in NMDA-sensitive [3H]glutamate, strychnine-insensitive [3H]glycine, [3H]spermidine, [3H]kainate or [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA) binding in any brain region 7 days after the last amygdala kindled seizure, or in the hippocampus 28 days after the last amygdala kindled seizure. These results indicate that [3H]MK-801 binding sites labeling NMDA-sensitive receptor-linked cation channels in the amygdala undergo downregulation only transiently, but that none of the subcomponents of the NMDA receptor macromolecular complex exhibit enduring changes at steady state following the completion of amygdala kindling.

Amygdala↗

PubMed1992

Inhibition of Na+,K(+)-ATPase activity by beta-eudesmol, a major component of atractylodis lanceae rhizoma, due to the interaction with enzyme in the Na.E1 state.

beta-Eudesmol, a major component of the crude drug "So-jutsu" (Atractylodis Lanceae Rhizoma), inhibited Na+, K(+)-ATPase activity most strongly among the various kinds of phosphatases examined. It also inhibited Ca(2+)-ATPase and H+, K(+)-ATPase, but to a lesser extent. Its effect on Mg(2+)-ATPase was minute. No effects on H(+)-ATPase or alkaline and acid phosphatase activities were observed. The effects of beta-eudesmol on horse kidney Na+, K(+)-ATPase were studied in detail, and the following results were obtained: (1) beta-eudesmol inhibited the Na+, K(+)-ATPase activity with an I50 value of 1.6 x 10(-4) M. The mode of its inhibition was uncompetitive with respect to ATP; (2) it prevented the stimulation of enzyme activity by Na+. The inhibition gradually increased in accord with the increase of Na+ concentration, and it was constant when Na+ was higher than 6.3 mM; (3) it did not alter the K+ concentration necessary for half-maximal activation (K0.5 for K+); and (4) it inhibited the enzyme activity with a mode of action different from ouabain. Phosphorylation of enzyme with [gamma-32P]ATP was inhibited by beta-eudesmol with an I50 of 1.4 x 10(-4) M. The inhibition was greater in 1 M NaCl than in 0.1 M NaCl. It had no effects on dephosphorylation steps, i.e. none of the non-specific, the ADP-sensitive (Na.E1-P----Na.E1) and the K(+)-dependent (E2-P----K.E2) dephosphorylation processes were affected. These results suggest that beta-eudesmol, a relatively specific inhibitor of Na+, K(+)-ATPase, interacts with the enzyme in the Na.E1 form and inhibits the reaction step Na.E1----Na.E1-P.

Adenosine Triphosphatases↗

PubMed1992

cDNA cloning, sequencing, expression and possible domain structure of human APEX nuclease homologous to Escherichia coli exonuclease III.

cDNA encoding the human homologue of mouse APEX nuclease was isolated from a human bone-marrow cDNA library by screening with cDNA for mouse APEX nuclease. The mouse enzyme has been shown to possess four enzymatic activities, i.e., apurinic/apyrimidinic endonuclease, 3'-5' exonuclease, DNA 3'-phosphatase and DNA 3' repair diesterase activities. The cDNA for human APEX nuclease was 1420 nucleotides long, consisting of a 5' terminal untranslated region of 205 nucleotide long, a coding region of 954 nucleotide long encoding 318 amino acid residues, a 3' terminal untranslated region of 261 nucleotide long, and a poly(A) tail. Determination of the N-terminal amino acid sequence of APEX nuclease purified from HeLa cells showed that the mature enzyme lacks the N-terminal methionine. The amino acid sequence of human APEX nuclease has 94% sequence identity with that of mouse APEX nuclease, and shows significant homologies to those of Escherichia coli exonuclease III and Streptococcus pneumoniae ExoA protein. The coding sequence of human APEX nuclease was cloned into the pUC18 SmaI site in the control frame of the lacZ promoter. The construct was introduced into BW2001 (xth-11, nfo-2) strain and BW9109 (delta xth) strain cells of E. coli. The transformed cells expressed a 36.4 kDa polypeptide (the 317 amino acid sequence of APEX nuclease headed by the N-terminal decapeptide derived from the part of pUC18 sequence), and were less sensitive to methylmethanesulfonate and tert-butyl-hydroperoxide than the parent cells. The N-terminal regions of the constructed protein and APEX nuclease were cleaved frequently during the extraction and purification processes of protein to produce the 31, 33 and 35 kDa C-terminal fragments showing priming activities for DNA polymerase on acid-depurinated DNA and bleomycin-damaged DNA. Formation of such enzymatically active fragments of APEX nuclease may be a cause of heterogeneity of purified preparations of mammalian AP endonucleases. Based on analyses of the deduced amino acid sequence and the active fragments of APEX nuclease, it is suggested that the enzyme is organized into two domains, a 6 kDa N-terminal domain having nuclear location signals and 29 kDa C-terminal, catalytic domain.

Amino Acid Sequence↗

PubMed1992

Detection of citrulline residues in deiminated proteins on polyvinylidene difluoride membrane.

We have developed a new detection method of deiminated proteins on polyvinylidene difluoride membranes. Citrulline residues in enzymatically deiminated histones were modified by incubating with diacetyl monoxime and antipyrine in a strong acid mixture. The products were injected to rabbits, and the antibodies obtained were affinity-purified using a modified citrulline column. Sample proteins blotted to the membrane were modified in a similar manner and incubated successively with the purified antibody and an alkaline phosphatase-conjugated second antibody. Detection was performed using a chemiluminescent substrate. The method enabled detection of 3-10 fmol of citrulline residues dot blotted as deiminated model proteins. It visualized numerous rat pituitary soluble proteins that had been enzymatically deiminated and Western blotted to the membrane. The data suggest usefulness of the method for detecting deiminated proteins regardless of the backbone protein molecules. Search for deiminated proteins on the Western blots of various rat tissue homogenates detected a single band on that of spinal cord, another band on that of uterus, and multiple bands on those of skin and hair root. The bands in the former two tissue homogenates comigrated with glial fibrillary acidic protein and vimentin, respectively.

Animals↗

PubMed1992

Processing in the 5' region of the pnp transcript facilitates the site-specific endonucleolytic cleavages of mRNA.

The primary transcript of pnp, the gene encoding polynucleotide phosphorylase in Escherichia coli, is processed in the 5' end region by ribonuclease III (RNase III). The unprocessed transcript shows enhanced stability compared with the processed transcript. We report here that, unlike the processed transcript, the unprocessed pnp transcript did not accept endonucleolytic attack at, at least, five cleavage sites. Sequencing analysis of the four cleavage products shows no sequence specific to all these sites, but AU rich stretches were observed at three sites.

Base Sequence↗

PubMed1992

Persistent supersensitivity of sigma receptors develops during repeated methamphetamine treatment.

Functional changes in sigma receptors were examined after behavioral sensitization induced by repeated methamphetamine treatment. Rats received either saline or 4 mg/kg methamphetamine for 14 days. (+)3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP), a sigma receptor agonist, was given as challenge after various periods of abstinence. (+)-3-PPP at doses greater than 6 mg/kg stimulated several forms of behavior in naive rats. (+)-3-PPP at 12 and 24 mg/kg produced more frequent rearing and more intense stereotyped sniffing and repetitive head movements in rats previously sensitized with methamphetamine than in saline-pretreated rats. The augmented response to (+)-3-PPP in methamphetamine-treated rats was maintained for at least one month. The augmented response to (+)-3-PPP was reversed by the combined administration of 100 mg/kg (+/-)-sulpiride, a D2 dopamine receptor antagonist, and 30 mg/kg BMY 14802, a sigma receptor antagonist. These results suggest that repeated methamphetamine treatment induces persistent supersensitivity in sigma receptors and that it may subsequently activate the dopamine system.

Animals↗

PubMed1992

Subchronic methamphetamine treatment enhances ouabain-induced striatal dopamine efflux in vivo.

The effect of manipulation of the Na+ gradient between the intracellular and extracellular media on striatal dopamine (DA) efflux under steady-state conditions after subchronic methamphetamine (MAP) treatment was investigated. Rats were injected with 4 mg/kg MAP or saline (i.p.), once daily for 14 days. Seven days after the last injection, ouabain (10(-4) M), a selective inhibitor of the Na+,K(+)-ATPase, was infused locally through a semi-permeable probe in the striatum. Ouabain induced a significantly greater (P less than 0.01) increase of the DA concentrations in the striatal perfusate in the subchronic MAP than the control group. The levels of 3,4-dihydroxyphenylacetic acid (DOPAC) (P less than 0.05) and 5-hydroxyindoleacetic acid (5-HIAA) (P less than 0.05) were significantly higher in the subchronic MAP than in the control group. Reserpine pretreatment (5 mg/kg, i.p.) did not affect the enhanced ouabain-induced DA efflux (P less than 0.01) in the subchronic MAP group, and the levels of DOPAC (P less than 0.01), 5-HIAA (P less than 0.01) and HVA (P less than 0.01) were also significantly higher in the subchronic MAP than in the control group. In contrast, alpha-methyl-p-tyrosine (250 mg/kg, i.p.) pretreatment abolished the ouabain-induced efflux of DA, DOPAC and HVA, but not 5-HIAA, in both groups. Specific striatal [3H]ouabain binding and striatal Na+,K(+)-ATPase activity in the subchronic MAP and control groups did not differ significantly. These results suggest that subchronic MAP treatment facilitates the efflux of newly synthesized DA, which is induced by the ouabain-induced decrease of the Na+ gradient between intracellular and extracellular media.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed1992

Long-lasting enhancement of metabotropic excitatory amino acid receptor-mediated polyphosphoinositide hydrolysis in the amygdala/pyriform cortex of deep prepiriform cortical kindled rats.

We have previously demonstrated that ibotenate (IBO)-stimulated polyphosphoinositide (PPI) hydrolysis is increased for a long period in the amygdala/pyriform cortex (AM/PC) of amygdala (AM)- and hippocampal (HIPP)-kindled rats. This finding indicates that enhanced function of the PPI-coupled excitatory amino acid (EAA) receptor may be associated with the long-lasting seizure susceptibility of kindling. The present study further examined PPI hydrolysis induced by trans-ACPD, a selective agonist of the metabotropic EAA receptor, as well as by IBO in brain slices of rats kindled from the deep prepiriform cortex (DPC). IBO-stimulated accumulation of [3H]inositol monophosphate ([3H]InsP) was significantly increased in the AM/PC by 162 (P less than 0.0001), 130 (P less than 0.005) and 81% (P less than 0.03) at 24 h, 7 days and 28 days, respectively, after the last kindled seizure, whereas it was increased significantly only at 24 h after the last seizure in the HIPP and did not change at any time in the limbic forebrain (LFB). The IBO-stimulated accumulation of [3H]InsP was significantly increased by 55% (P less than 0.01) in the AM/PC of partially kindled rats reaching an average stage of 3.7, but not in the AM/PC of those remaining at stage 1, 7 days after the last kindled seizure. Trans-ACPD-stimulated PPI hydrolysis was significantly increased in the AM/PC of DPC-kindled rats by 65 (P less than 0.05) and 45% (P less than 0.005) at 7 and 28 days, respectively, after the last kindled seizure. Cis-ACPD-stimulated PPI hydrolysis was also significantly increased in the AM/PC of DPC-kindled rats by 45 (P less than 0.03) and 30% (P less than 0.04) at 7 and 28 days, respectively, after the last seizure. There was no increase in trans-ACPD- or cis-ACPD-stimulated PPI hydrolysis in the HIPP or LFB. These results further confirm our previous studies showing that the metabotropic EAA receptor-stimulated PPI hydrolysis exhibited a long-lasting increase in the AM/PC irrespective of the primary stimulation site for kindling.

Amygdala↗

PubMed1992

Characterization of N-myc amplification in a human neuroblastoma cell line by clones isolated following the phenol emulsion reassociation technique and by hexagonal field gel electrophoresis.

The N-myc amplification of human neuroblastomas was characterized by the amplified DNA cloned from the cell line MC-NB-1 using the phenol emulsion reassociation technique (PERT). A number of PERT clones exhibiting amplification in this cell line were tested for amplification in other neuroblastoma cell lines. In almost all cell lines examined, only a few clones were co-amplified with N-myc and most of the others were exclusively amplified in a subset of the cell lines. The total aggregate size of the Hind III fragment identified by the PERT clones was approximately 350 kb. Most of the PERT clones were mapped to human chromosome (chr) 2p23-2pter, where the N-myc gene is located. Four types of amplicons, the 100, 420, 480 and 520 kb fragments, shown to be Not I fragments, were identified by hexagonal field gel electrophoresis. Three fragments are ordered in a head-to-tail array, and the remaining fragment is either ordered in a tail-to-head array or something else. Despite the extremely unusual construction of the amplified sequences in this cell line as compared with others, there was a low degree of sequence heterogeneity among the amplicons within this cell line. These observations lead to the idea that the complex rearrangements that give rise to the heterogeneous organization of the amplified sequences among the different cell lines precede the amplification of these sequences.

Chromosomes, Human, Pair 2↗

PubMed1992

2-Guanidinoethanol increased dopamine release and 3,4-dihydroxyphenylacetic acid content, but not homovanillic acid content in the rat brain: electroneurochemical and enzymological studies.

The effects of 2-guanidinoethanol (GEt) on the release of monoamines and on the activity of their degrading enzymes were studied in order to investigate why 3,4-dihydroxyphenylacetic acid (DO-PAC) increased to a much greater extent than homovanillic acid (HVA) after GEt injection into rat brain. In differential pulse voltammograms recorded using an electrochemically treated carbon fiber electrode, two distinct oxidation peaks, one at 130mV (DOPAC peak) and the other at 300 mV (5-hydroxyindoleacetic acid (5-HIAA) peak), were observed. In the hippocampus, the DOPAC peak increased markedly compared to the peak height recorded prior to the intracerebroventricular injection of GEt (6 mumol). Although the DOPAC peak height increased to 350% 4 hours after GEt injection, the 5-HIAA peak showed no change. In the striatum, the DOPAC peak increased to 150% 3 hours after GEt injection. Serial changes in the extracellular levels of DOPAC, HVA, and 5-HIAA were monitored in the striatum after GEt injection, using an in vivo brain micro-dialysis technique. Although the DOPAC levels strated to increase 80 minutes after GEt injection, HVA and 5-HIAA levels showed no change. On the other hand, monoamineoxidase, which metabolizes dopamine to DOPAC, was not activated and catechol-O-methyltransferase, which metabolizes DOPAC to HVA, were not inhibited by 5 mM of GEt in vitro. These data suggested that GEt increased the release of dopamine, but not of serotonin, and that GEt might restrict the DOPAC transport system.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1992

BMY-14802 reverses the reduction of striatal dopamine release induced by (+)-3-[3-hydroxyphenyl]-N-(1-propyl)piperidine.

Intraperitoneal injection of (+)-3-[3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3PPP), a sigma receptor agonist, significantly reduced the striatal levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) measured by in vivo microdialysis. These reductions were significantly greater at (+)-3PPP doses of 12 and 24 mg/kg than at 1 mg/kg. The levels of 5-hydroxyindoleacetic acid (5HIAA) were increased by the injection of (+)-3PPP in dose of 24 mg/kg, but were not affected at lower doses. BMY-14802, a sigma antagonist, alone at doses of 15 mg/kg and 30 mg/kg did not affect the levels of DA, DOPAC, HVA and 5HIAA. Pretreatment with 30 mg/kg BMY-14802 reversed the reduction of the levels of DA induced by 12 mg/kg (+)-3PPP. Although neither 30 mg/kg BMY-14802 nor 12 mg/kg (+)-3PPP affected the levels of striatal 5HIAA, combined treatment with both produced a significant elevation. These findings clearly demonstrate that sigma receptors may regulate DA release from the striatal presynapse.

Animals↗

PubMed1992

Peripheral acting muscle relaxants alter the effects of baclofen on the electrocorticograms in the rat.

The effects of intraperitoneally administered baclofen on behavior and electrocorticograms (ECoG) were studied in freely moving and paralyzed rats. In the freely moving rats, 10 mg/kg of baclofen suppressed ECoGs with behavioral sedation, and 20 mg/kg caused whole body twitching accompanied with spike discharges in low voltage slow waves background. In the freely moving rats, baclofen acted as depressant in low dose and convulsant in high dose. In the paralyzed rat, 10 mg/kg of baclofen first suppressed ECoGs. Though fast waves components recovered with slow waves background in the ECoGs of rats paralyzed with gallamine (50 mg/kg) 3 hours after the baclofen injection, fast waves activities were not observed in the ECoG of rats paralyzed with succinylcholine (50 mg/kg), d-tubocurarine (3 mg/kg) or pancuronium (1 mg/kg). Under paralysis with d-tubocurarine, baclofen suppressed ECoG first, and then spike discharges started 90 min after the injection. These results suggest that the effects of baclofen on ECoG were different depending on the muscle relaxant used.

Animals↗

PubMed1992

Supersensitivity of sigma receptors after repeated administration of cocaine.

We investigated the role of sigma receptors in the expression of behavioral sensitization induced by cocaine. Rats received intraperitoneal injections of either 20 mg/kg cocaine or saline once daily for 14 consecutive days. Cocaine-treated rats became sensitized. After a 5-day abstinence period, a challenge dose of (+)-3-[3-hydroxyphenyl]-N-(1-propyl)piperidine ((+)-3-PPP), a sigma receptor agonist, was administered. (+)-3-PPP at doses of 12 and 24 mg/kg induced significantly more frequent rearing and more potent stereotypy consisting of repetitive head movement and sniffing in cocaine-sensitized rats than in saline-pretreated rats. These enhanced responses to (+)-3-PPP lasted for at least a month. The enhanced responses to (+)-3-PPP were attenuated by 30 mg/kg BMY 14802, a putative sigma antagonist, and also attenuated by 100 mg/kg (+/-)-sulpiride, a D2 dopamine antagonist. These findings show that repeated administration of cocaine produces lasting supersensitivity of simga receptors, which may induce subsequent activation of dopaminergic transmission.

Animals↗

PubMed1992

Competitive and non-competitive N-methyl-D-aspartate antagonists fail to prevent the induction of methamphetamine-induced sensitization.

In order to elucidate the possible roles of the glutamate system in the mechanisms underlying behavioral sensitization, which is used as an animal model for human psychosis, we investigated the effects of 3-((+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) and MK-801 ((+)-dizocilpine), a competitive and noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, respectively, on methamphetamine-induced behavioral sensitization in rats. Administration of 0.5 mg/kg MK-801 enhanced 2 mg/kg methamphetamine-induced hyperactivity, whereas it reduced 6 mg/kg methamphetamine-induced stereotyped behavior markedly. CPP (10 mg/kg) reduced 2 mg/kg methamphetamine-induced stereotypy slightly. Repeated treatment with 2 and 6 mg/kg methamphetamine alone induced progressive augmentation of stereotypy, whereas combining either MK-801 or CPP with methamphetamine treatment abolished or attenuated this augmentation. However, when rats were challenged with methamphetamine after a 7-day period of abstinence, the intensity of stereotypy among the rats pretreated with repeated doses of methamphetamine alone or in combination with MK-801 or CPP did not differ significantly. These results indicate that competitive and non-competitive NMDA receptor antagonists modulate acute methamphetamine-induced abnormal behavior and sensitization expression, but they failed to prevent the induction of the neural mechanisms underlying behavioral sensitization.

Animals↗

PubMed1992

Sigma (sigma) antagonist BMY 14802 prevents methamphetamine-induced sensitization.

We have demonstrated for the first time that the sigma antagonist BMY 14802 prevents the development of behavioral sensitization induced by repeated administration of methamphetamine. Rats received an intraperitoneal injection of 15 or 30 mg/kg BMY 14802 followed by 2 mg/kg methamphetamine 30 min later. Unlike dopamine antagonists, BMY 14802 did not induce major changes in the acute motor effects of 2 mg/kg methamphetamine. Repeated administration of methamphetamine induced progressive augmentation of stereotyped behaviors and resulted in behavioral sensitization. However, repeated administration of methamphetamine in combination with BMY 14802 at either dose produced no increase in the intensity of stereotypy when compared with the first treatment. After a 7-day abstinence period, a challenge test with methamphetamine alone revealed supersensitivity of methamphetamine-sensitized rats to subsequent methamphetamine, whereas rats pretreated with repeated methamphetamine in combination with BMY 14802 exhibited no difference in the intensity of stereotypy from rats pretreated with repeated saline. These results suggest that sigma receptors play a crucial role in the induction of methamphetamine-induced sensitization.

Animals↗

PubMed1992

The effect of convulsions on the rectification of central nervous system disorders in epileptic mice.

Abnormal behavior in epileptic mice (El mice) may be rectified after convulsive seizures. This mechanism was investigated behaviorally through measurements of ethanol-induced sleeping time and locomotor activity, as well as immunohistochemically using a microphotometry system. Decreased ethanol-induced sleeping time and increased ethanol-dependent locomotor activity in El mice as compared to ddY mice (the mother strain of El mice) were rectified by convulsions as well as the intraventricular (IVT) administration of CaCl2, dopamine, or serotonin. Also, the lower dopamine levels in the neostriatum and nucleus accumbens septi in El mice as compared to ddY mice were improved by convulsions as well as the IVT administration of CaCl2. We have previously observed that a lower level of serum calcium in El mice causes a decrease in central biogenic amine synthesis through a calmodulin-dependent system. This may increase the susceptibility to epileptic convulsions and induce abnormal behavior. Combining the present results with our previous observations, we suggest that the convulsions in El mice will be induced when the balance of physiological functions is lost, as may be seen when the biogenic amine syntheses are decreased. The serum calcium level in El mice is increased by convulsions, and an elevated serum calcium level enhances brain biogenic amine synthesis through a calmodulin-dependent system. Subsequently, biogenic amines rectify physiological disorders in El mice.

Animals↗

PubMed1992

Voluntary intake of alcohol is attenuated by ipsapirone in mice and role of 5-HT1A receptor.

Emerging evidences have suggested that the brain serotonin (5-hydroxytryptamine, 5-HT) neurotransmitter system is involved in the compulsive alcohol-seeking behaviors in humans and animal models. The aim of this study is to examine the effect of ipsapirone, which is a specific 5-HT1A agonist with a pyrimidinylpiperazine structure, on alcohol consumption in mice (C57BL/6J) by a voluntary alcohol intake paradigm. When the consumed alcohol was expressed as g/kg B.W., the total 12-day amount was significantly lower in the ipsapirone-treated mice than in the saline-treated mice. However, 5-HT1A receptor binding sites labeled with [3H]8-OH-DPAT in hippocampal membranes did not differ significantly in either the total number of binding sites (Bmax) or dissociation constant (Kd) between the two groups. The possible mechanism regarding the role of ipsapirone that attenuated the alcohol consumption, and its relationship to the subtyping 5-HT receptors are further discussed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗