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I Sora

Publications and source records attributed to I Sora.

At least 55 records · Page 3Linked to original sources
PubMed1998

No heroin or morphine 6beta-glucuronide analgesia in mu-opioid receptor knockout mice.

Recent reports suggest that heroin and its metabolite morphine 6beta-glucuronide can produce analgesia independent of the morphine-preferring mu-opioid receptor. We have tested heroin and morphine 6beta-glucuronide analgesia in wild-type, homozygous and heterozygous mu-opioid receptor knockout mice. Homozygotes display no heroin or morphine 6beta-glucuronide analgesia. Heterozygous mice with one mu-opioid receptor gene copy reveal reduced heroin and morphine 6beta-glucuronide analgesia. The mu-opioid receptor-dependence of heroin and morphine 6beta-glucuronide fails to support a requirement for a heroin-specific opiate receptor subtype.

Analgesia↗
PubMed1998

Cocaine reward models: conditioned place preference can be established in dopamine- and in serotonin-transporter knockout mice.

Cocaine and methylphenidate block uptake by neuronal plasma membrane transporters for dopamine, serotonin, and norepinephrine. Cocaine also blocks voltage-gated sodium channels, a property not shared by methylphenidate. Several lines of evidence have suggested that cocaine blockade of the dopamine transporter (DAT), perhaps with additional contributions from serotonin transporter (5-HTT) recognition, was key to its rewarding actions. We now report that knockout mice without DAT and mice without 5-HTT establish cocaine-conditioned place preferences. Each strain displays cocaine-conditioned place preference in this major mouse model for assessing drug reward, while methylphenidate-conditioned place preference is also maintained in DAT knockout mice. These results have substantial implications for understanding cocaine actions and for strategies to produce anticocaine medications.

Animals↗
PubMed1997

VMAT2 knockout mice: heterozygotes display reduced amphetamine-conditioned reward, enhanced amphetamine locomotion, and enhanced MPTP toxicity.

The brain vesicular monoamine transporter (VMAT2) pumps monoamine neurotransmitters and Parkinsonism-inducing dopamine neurotoxins such as 1-methyl-4-phenyl-phenypyridinium (MPP+) from neuronal cytoplasm into synaptic vesicles, from which amphetamines cause their release. Amphetamines and MPP+ each also act at nonvesicular sites, providing current uncertainties about the contributions of vesicular actions to their in vivo effects. To assess vesicular contributions to amphetamine-induced locomotion, amphetamine-induced reward, and sequestration and resistance to dopaminergic neurotoxins, we have constructed transgenic VMAT2 knockout mice. Heterozygous VMAT2 knockouts are viable into adult life and display VMAT2 levels one-half that of wild-type values, accompanied by smaller changes in monoaminergic markers, heart rate, and blood pressure. Weight gain, fertility, habituation, passive avoidance, and locomotor activities are similar to wild-type littermates. In these heterozygotes, amphetamine produces enhanced locomotion but diminished behavioral reward, as measured by conditioned place preference. Administration of the MPP+ precursor N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to heterozygotes produces more than twice the dopamine cell losses found in wild-type mice. These mice provide novel information about the contributions of synaptic vesicular actions of monoaminergic drugs and neurotoxins and suggest that intact synaptic vesicle function may contribute more to amphetamine-conditioned reward than to amphetamine-induced locomotion.

Amphetamine↗
PubMed1997

The mu-opioid receptor is necessary for [D-Pen2,D-Pen5]enkephalin-induced analgesia.

Interactions between delta-opioid receptors and morphine-preferring mu-opioid receptor subtypes have been suggested. Availability of transgenic mu-opioid receptor knockout mice allows assessment of mu-opioid receptor roles in the analgesia produced by the classical delta-opioid receptor agonist [D-Pen2,D-Pen5]enkephalin (DPDPE) in hot-plate and tail-flick tests. DPDPE analgesia was dramatically reduced in mu-opioid receptor knockout mice in a gene-dose-dependent fashion. The analgesia induced by this classic delta-opioid receptor agonist depends on intact mu-opioid receptors, suggesting that selective delta-opioid receptor drugs may require mu-opioid receptor occupancies for full efficacy.

Analgesia↗
PubMed1997

Opiate receptor knockout mice define mu receptor roles in endogenous nociceptive responses and morphine-induced analgesia.

Morphine produces analgesia at opiate receptors expressed in nociceptive circuits. mu, delta, and kappa opiate receptor subtypes are expressed in circuits that can modulate nociception and receive inputs from endogenous opioid neuropeptide ligands. The roles played by each receptor subtype in nociceptive processing in drug-free and morphine-treated states have not been clear, however. We produced homologous, recombinant mu, opiate receptor, heterozygous and homozygous knockout animals that displayed approximately 54% and 0% of wild-type levels of mu receptor expression, respectively. These mice expressed kappa receptors and delta receptors at near wild-type levels. Untreated knockout mice displayed shorter latencies on tail flick and hot plate tests for spinal and supraspinal nociceptive responses than wild-type mice. These findings support a significant role for endogenous opioid-peptide interactions with mu opiate receptors in normal nociceptive processing. Morphine failed to significantly reduce nociceptive responses in hot plate or tail flick tests of homozygous mu receptor knockout mice, and heterozygote mice displayed right and downward shifts in morphine analgesia dose-effect relationships. These results implicate endogenous opioid-peptide actions at mu opiate receptors in several tests of nociceptive responsiveness and support mu receptor mediation of morphine-induced analgesia in tests of spinal and supraspinal analgesia.

Analgesia↗
PubMed1994

The cloning and expression of a human creatine transporter.

A human creatine transporter (hCRT-BS2M) cDNA clone was isolated from a human brainstem/spinal cord using a PCR and phage plaque hybridization based technique. This clone included an open reading frame of 1,905 base pairs(bp) within a 2,283bp cDNA. Northern blot hybridization detected the expression of corresponding mRNAs most prominently in the skeletal muscle, heart and kidney. Peptide sequence analysis of the hCRT-BS2M protein product revealed 12 putative transmembrane domains. The predicted protein sequence further demonstrates that the hCRT-BS2M has highly conserved amino acid identity with the other members of the sodium dependent plasma membrane transporter family. Transient expression of the hCRT-BS2M in COS-7 cells demonstrates sodium dependent [14C]creatine uptake with a KM value of 14.9 +/- 3.0 microM (n = 5) that is attenuated by creatine and selective structural analogues of creatine.

Amino Acid Sequence↗
PubMed1993

Characterization of a cloned rat serotonin 5-HT1A receptor expressed in the HeLa cell line.

We have previously isolated the rat serotonin (5-HT)1A receptor gene (G21Y2) and now report the expression and characterization of this receptor. The BamHI/Xbal fragment of this gene was cloned into Rc/RSV and stably transfected into HeLa cells by the calcium phosphate method. For determination of specific 5-HT1A receptor binding, [3H]8OH-DPAT was used as the radioligand and incubated with HeLa cell membranes. The cells expressed specific and saturable binding of [3H]8OH-DPAT with a Kd value of 0.3 nM and a Bmax value of 2 pmol/mg protein. GTP (50 microM) added to the incubation mixture increased the Kd value to 3 nM indicating that the expressed receptor is coupled to a G protein. The specific binding was inhibited by selective 5-HT1A partial agonists, such as buspirone, ipsapirone, gepirone, tandospirone, zalospirone and SUN8399 with Ki values of 1-30nM, whereas other neurotropic drugs except for spiperone (Ki = 46 nM) and nemonapride (Ki = 2.3 nM) were effective only at concentrations of more than 100 microM. The potencies of these compounds to inhibit [3H]8OH-DPAT from its specific binding sites were similar to their affinities determined in rat hippocampus binding studies. These data suggest that the expressed receptor is a 5-HT1A-type similar to 5-HT1A receptors in the rat hippocampus.

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

Lack of effect of haloperidol or methamphetamine treatment on the mRNA levels of two dopamine D2 receptor isoforms in rat brain.

In order to investigate whether changes of the two mRNAs encoding the D2 receptor isoforms were induced by chronic haloperidol or methamphetamine treatment in rats, we measured the brain mRNA levels using in situ hybridization histochemistry (ISHH). We used two oligonucleotide probes, an "insert" probe to hybridize with the longer D2 receptor, D2(444), mRNA, and a "spanning" probe to hybridize with the shorter D2 receptor, D2(415), mRNA. Both D2 mRNAs were detected by ISHH in the caudate putamen, nucleus accumbens, substantia nigra, pars compacta and ventral tegmental area. The distributions and the amounts of the mRNAs for the two D2 isoforms did not change after chronic administration of haloperidol (1 mg/kg/day for 14 days, ip) or methamphetamine (4 mg/kg/day for 14 days, ip). These results suggest that the changes of D2 receptor density induced by chronic neuroleptic and psychostimulant treatment are not due primarily to receptor expression.

Animals↗
PubMed1991

Localization of the mRNAs for two dopamine D2 receptor isoforms in the rat brain.

Two molecular forms of the dopamine D2 receptor were generated by alternative RNA splicing. To investigate the relative distributions of the two mRNAs encoding the D2 receptor isoforms, D2(415) and D2(444), we performed in situ hybridization histochemistry in the rat brain with the two oligonucleotide probes. An insert probe complementary to an additional fragment of the D2 receptor mRNA cloned from the rat brain, and a spanning probe complementary to its contiguous sequence were used. These 48 base probes were 3'-end labeled with [35S]dATP. The brains were dissected from male SD rats and frozen in dry ice and acetone. Cryostat sections (16 microns) were collected on gelatin coated slides and stored at -20 degrees C. In situ hybridization studies were conducted with a probe concentration of 1 x 10(6) dpm/100 microliters of buffer per brain slice at 37 degrees C for 18-20 h in a humid chamber. The slides were washed, dried and exposed to tritium sensitive film for one week. The autoradiograph showed that both mRNA were present at high levels in the corpus striatum, accumbens nucleus and substantia nigra (pars compacta). Identical patterns of labeling were obtained in the rat brain using both the insert and spanning probes, although the optical densities detected with the insert probe were higher than those with the spanning probe in the corpus striatum. This suggests that both D2 receptor mRNAs are expressed similarly in each region of the rat brain and D2(444) expressed dominantly in the corpus striatum.

Animals↗
PubMed1991

Long-lasting enhancement of the membrane-associated protein kinase C activity in the hippocampal kindled rat.

We demonstrated that only membrane-associated protein kinase C (PKC) activity increased in the bilateral hippocampus (HIPP) up to 4 weeks and in the amygdala/pyriform cortex (AM/PC) at 4 weeks after the last kindled seizure. The enhancement of the membrane-associated PKC activity exceeds the increase in the protein concentration, which was observed in part. The overwhelming increase in the PKC activity should be of significance in the long-term maintenance of the kindling phenomenon.

Animals↗
PubMed1991

[The molecular biology of dopamine receptors].

In this article advances in the molecular biology of dopamine receptors are reviewed. Dopamine receptor subtypes D1, D2 and D3 have been cloned and characterized over the last three years. Analysis of their amino acid sequences has shown that these subtypes belong to the G protein-coupled receptor family, with seven transmembrane domains, a C-terminus within the cell and a N-terminus outside the cell. The distribution of mRNAs coding these receptors was determined by Northern blotting or in situ hybridization, and they were expressed in eukaryotic cells for application in such pharmacological experiments as receptor binding and cAMP accumulation. D1 receptors, which have 446 amino acids, were expressed in cells and detected by [3H]SCH23390 binding and cAMP accumulation assay. However, another paper described D1 as having 485 amino acids and suggested the existence of D1 receptor subclasses. D2 receptors have two isoforms, D2 (444) and D2(415), produced by alternative RNA splicing. D2 (444) has 29 additional amino acids in the third intracellular loop of D2(415). The mRNA distribution differs between D2 (444) and D2 (415), although the pharmacological profiles of the two isoforms are identical. The D3 receptor is localized in the limbic area of the brain and has a relatively high affinity for atypical neuroleptics and putative autoreceptor-selective agents. D3 appears to mediate some of the antipsychotic effects of the agents.

Animals↗
PubMed1987

Alterations of the muscarinic cholinergic (mACh) receptors in the striatum of the MPTP-induced parkinsonian model in mice: in vitro quantitative autoradiographical analysis.

The alteration of muscarinic cholinergic (mACh) receptors in the striatum of mice after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was examined using a [3H]quinuclidinyl benzilate [( 3H]QNB) in vitro labeling macro-autoradiographic technique and mACh receptor concentration was quantitatively analyzed using a computer analysis system. Two weeks after cessation of MPTP administration, the striatal mACh receptors were significantly increased. In the subchronic phase, at 6 weeks, the striatal mACh receptors were significantly decreased but recovered to the normal level by the treatment with L-dihydroxyphenylalanine (L-DOPA) for two weeks before sacrifice. These findings indicated that the striatal mACh receptors are strongly regulated by the nigrostriatal dopaminergic function.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Chronic dihydroergotoxine administration increases muscarinic cholinergic receptor binding in aged-rat brain.

Changes in the distribution and densities of muscarinic cholinergic receptors (mCh-R) and the effects of dihydroergotoxine (DHET) administration on these changes were studied in the aged-rat brain by in vitro autoradiography. mCh-R binding in the brain was markedly reduced in aged rats as compared with young adult rats, but chronic administration of DHET specifically recovered mCh-R binding in the temporal cortex and hippocampus.

Aging↗
PubMed1986

Dexamethasone suppression test and noradrenergic function in affective and schizophrenic disorders.

The relationship between hypothalamic-pituitary-adrenal (HPA) function and the noradrenergic system was examined in patients with affective and with schizophrenic disorders. In response to the Dexamethasone Suppression Test (DST), serum cortisol, plasma catecholamine levels, and serum creatine kinase (CK) activity were measured. Among patients with major depression, those with higher post-DST cortisol levels had higher plasma catecholamine levels and lower serum CK activity. Among acute schizophrenic patients, those with higher serum CK activity had higher baseline and post-DST cortisol levels. These results indicate that in both major depression and in acute schizophrenia, there is a dysfunction of the HPA axis and the noradrenergic system, but the noradrenergic dysfunctions are different in the two disorders.

Acute Disease↗
PubMed1983

[A study of incidence and symptoms in 71 patients with cavum septi pellucidi].

Seventy one patients with cavum septi pellucidi (CSP) were found among 2722 patients who had received computerized tomographic scanning. A clinical evaluation of these patients was made to examine incidence, clinical symptoms and neurological signs of CSP. The results obtained were as follows: 1) Incidence of CSP was 2.6% of the patients who visited outpatient clinic of a mental hospital. Sex ratio was M:F 1.9:1.0. 2) Age of onset of chief complaints mainly ranged from 10 to 30 years in male, and 10 to 60 years in female. 3) Complications of epileptic attacks and mental retardation were 22.5% and 9.9% of the patients with CSP, respectively. Frequency of these complications was significantly higher, as compared with the patients without CSP. 4) Chief complaints of the patients with CSP were; headache (43.1%), nausea and/or vomiting (23.8%), epileptic attacks (22.5%), dizziness (19.7%) and emotional instability (19.7%). 5) No neurological signs specific to CSP was found in this study. 6) EEG abnormality was found in 22 of 71 patients with CSP.

Adolescent↗