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N Hiroi

Publications and source records attributed to N Hiroi.

50 records · Page 3Linked to original sources
PubMed1995

Differences in down-regulation of glucocorticoid receptor mRNA by cortisol, prednisolone and dexamethasone in HeLa cells.

Glucocorticoids regulate the levels of their cognate receptors in a number of target tissues and in many different cell lines. We have compared the effect of three glucocorticoids, cortisol and its synthetic derivatives, prednisolone an dexamethasone, on the levels of glucocorticoid receptor (GR) mRNA in HeLa cells. Clinically, the synthetic derivatives are more active in hormonal action and have a longer half-life than cortisol. In the present study, the amounts of GR mRNA in HeLa cells were examined by Northern blot hybridization after treatment with cortisol, prednisolone or dexamethasone. These glucocorticoids decreased GR mRNA levels differently. After 24 h treatment with 1 x 10(-5) M cortisol, GR mRNA levels were only marginally suppressed (90% of the control), while prednisolone and dexamethasone suppressed GR mRNA levels to 67 and 57%, respectively. These differences may relate to the biological activities of these glucocorticoids. In time course studies, GR mRNA levels of the cells treated with cortisol and prednisolone decreased to the minimum levels within 4 h and then recovered gradually, while those treated with dexamethasone reached the minimum level at 8 h and remained suppressed for more than 24 h. These differences may relate to the biological half-lives of these glucocorticoids.

Anti-Inflammatory Agents↗
PubMed1995

Regulation of delta FosB and FosB-like proteins by electroconvulsive seizure and cocaine treatments.

Previous work has shown that c-Fos and several Fos-like proteins or Fras (Fos-related antigens) are induced acutely in brain in response to a wide variety of stimuli. In contrast, several stimuli induce apparently distinct Fos-like proteins, termed chronic Fras, after chronic administration. We show that delta FosB, a truncated splice variant of FosB, responds like the other acute Fras: it is induced rapidly and transiently in cerebral cortex after acute electroconvulsive seizure (ECS) and in striatum after acute cocaine but does not accumulate after chronic ECS or cocaine treatment. Although the chronic Fras are immunochemically related to delta FosB, they can be distinguished from delta FosB based on their temporal properties in that they are induced after chronic ECS and cocaine treatments only. Moreover, the chronic Fras and delta FosB can be distinguished by their migration patterns on one- and two-dimensional gel electrophoresis. The chronic Fras, therefore, appear to be novel FosB-related proteins. We also provide evidence that the chronic Fras heterodimerize primarily with Jun-D and Jun-B, as opposed to c-Jun. The possibility that AP-1 complexes containing the chronic Fras function as negative regulators of AP-1 mediated transcription is discussed.

Amino Acid Sequence↗
PubMed1994

Dopamine D1 receptor mutant mice are deficient in striatal expression of dynorphin and in dopamine-mediated behavioral responses.

The brain dopaminergic system is a critical modulator of basal ganglia function and plasticity. To investigate the contribution of the dopamine D1 receptor to this modulation, we have used gene targeting technology to generate D1 receptor mutant mice. Histological analyses suggested that there are no major changes in general anatomy of the mutant mouse brains, but indicated that the expression of dynorphin is greatly reduced in the striatum and related regions of the basal ganglia. The mutant mice do not respond to the stimulant and suppressive effects of D1 receptor agonists and antagonists, respectively, and they exhibit locomotor hyperactivity. These results suggest that the D1 receptor regulates the neurochemical architecture of the striatum and is critical for the normal expression of motor activity.

Analysis of Variance↗
PubMed1993

The ventral pallidum area is involved in the acquisition but not expression of the amphetamine conditioned place preference.

The present study examined the roles of the ventral pallidum area, one output system of the nucleus accumbens, in the acquisition and expression of the amphetamine conditioned place preference (CPP). Pre-conditioning NMDA lesions of the ventral pallidum area completely abolished the acquisition of the CPP. By contrast, post-conditioning NMDA lesions of the same area had no effect on the expression of the CPP. These results suggest that the ventral pallidum area mediates some process that involves the primary, but not conditioned rewarding effects of amphetamine.

Analysis of Variance↗
PubMed1993

[Acromegaly].

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Acromegaly↗
PubMed1992

Pipradrol conditioned place preference is blocked by SCH23390.

We investigated the effect of the selective D1 dopamine antagonist, SCH23390, on the establishment of a pipradrol-conditioned place preference (CPP). Among various doses of pipradrol (6.25-75.0 mg/kg, SC), a CPP was established at 25.0 mg/kg. SCH23390 (0.16 mg/kg, IP) blocked the establishment of a CPP by this dose of pipradrol. The results suggest that pipradrol produces a rewarding effect and that this effect may involve activation of D1 dopamine receptors.

Animals↗
PubMed1991

The amphetamine conditioned place preference: differential involvement of dopamine receptor subtypes and two dopaminergic terminal areas.

We investigated involvement of dopamine receptor subtypes and two dopaminergic terminal areas in the acquisition and the expression of the amphetamine conditioned place preference (CPP). When injected systemically before conditioning, both D1 and D2 dopamine antagonists blocked acquisition in a dose-dependent manner. When injected systemically before testing, the effects of the same D1 and D2 antagonists differed. The selective D1 antagonist SCH23390 dose-dependently blocked expression of the previously established conditioned behavior within the dose range that also blocked acquisition. In contrast, D2 antagonists failed to block expression of the amphetamine CPP at doses which blocked acquisition. Expression was, however, blocked by higher doses of D2 antagonists, which may have lost their selectivity for the D2 dopamine receptor. The expression of the CPP was also blocked by microinjections of SCH23390 or sulpiride into nucleus accumbens, but not into striatum. In a control experiment, sodium pentobarbital, which significantly reduced spontaneous locomotor activity in a manner similar to the higher doses of the dopamine antagonists, had no effect on the expression of the amphetamine CPP when given before testing. Finally, electrolytic lesions of the dorsal striatum potentiated the amphetamine CPP. These findings indicate that the dopamine released by amphetamine interacts with both D1 and D2 dopamine receptors to establish a CPP, but that the expression of the CPP may involve activation of the D1 dopamine receptor in the nucleus accumbens.

Animals↗
PubMed1991

Place conditioning with dopamine D1 and D2 agonists injected peripherally or into nucleus accumbens.

The conditioned place preference technique was used to assess the affective properties of the direct dopamine D1 agonist, SKF38393, and the direct D2 agonist, LY171555 (quinpirole). A three compartment apparatus was used: the animals' pre-experimental preference for the two choice compartments was equal and, within each experimental group, half the rats received drug pairings in each choice compartment. Intraperitoneal injections of SKF38393 produced conditioned place aversions at all doses tested (1.0-4.0 mg/kg); LY171555 produced weak conditioned place preferences at 1.0 and 2.0 mg/kg, but no reliable effect at 4.0 mg/kg. Bilateral intra-accumbens microinjections of SKF38393 produced strong preferences at all doses tested (0.5-2.0 micrograms/side); LY171555 produced strong preferences at two doses (0.5 and 1.0 micrograms/side) and no effect at a third dose (2.0 micrograms/side). These results suggest that activation of either D1 or D2 receptors in the nucleus accumbens can produce reward, and that D1 receptors (and possibly also D2 receptors) located elsewhere in the brain or in the periphery may mediate aversive effects.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

The lateral nucleus of the amygdala mediates expression of the amphetamine-produced conditioned place preference.

We investigated the involvement of the hippocampal formation and the amygdala in the acquisition and expression of the amphetamine-produced conditioned place preference (CPP). Animals were conditioned in four sessions that included two pairings of d-amphetamine (2.0 mg/kg, s.c.) with one of two distinct compartments and two pairings of vehicle with the other compartment in a counterbalanced manner. Animals' preferences for the compartments were then tested in the absence of amphetamine. The CPP was attenuated by preconditioning electrolytic or excitotoxic lesions of the lateral nucleus of amygdala, but not by electrolytic lesions of the central or basolateral nucleus of amygdala, endopiriform nucleus, or ventral hippocampus or by radio-frequency lesions of the fornix-fimbria. When the lateral nucleus of amygdala was damaged by electrolytic or excitotoxic lesions after conditioning, animals failed to express an amphetamine-produced CPP. These results demonstrate that expression of the amphetamine-produced CPP is mediated by intrinsic neurons of the lateral nucleus of the amygdala, and that neither acquisition nor expression of the CPP is mediated by the central or basolateral amygdaloid nucleus or the hippocampus-accumbens projection. Combined with our previous finding that the expression of the amphetamine-produced CPP is also mediated by dopamine receptor activation in the nucleus accumbens (Hiroi and White, 1989, 1990), it could be suggested that the lateral nucleus of the amygdala and dopamine terminals in the nucleus accumbens are parts of the neural circuitry that mediates the expression of the amphetamine-produced CPP.

Amphetamine↗
PubMed1990

The reserpine-sensitive dopamine pool mediates (+)-amphetamine-conditioned reward in the place preference paradigm.

The neural basis of amphetamine-conditioned reward was investigated in the conditioned place preference paradigm. When bilaterally injected into the nucleus accumbens before the test session, a dopamine receptor blocker, alpha-flupenthixol, blocked the expression of the amphetamine-conditioned place preference. alpha-Flupenthixol had no significant effect on spontaneous locomotor activity. Bilateral microinjections of a tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine (alpha-MPT), decreased (+)-amphetamine locomotor stimulation in a dose-dependent fashion. Two doses of alpha-MPT that completely blocked (+)-amphetamine locomotor stimulation had no effect on the expression of the conditioned place preference when injected into the nucleus accumbens before testing. Reserpine administered subcutaneously before testing blocked the expression of the conditioned place preference. A dose of reserpine (4.0 mg/kg), which completely blocked the conditioned place preference, did not attenuate (+)-amphetamine-induced locomotor stimulation. This dose of reserpine depleted dopamine in the nucleus accumbens to 4% of its normal value. These data show that (+)-amphetamine-conditioned reward, expressed as a conditioned place preference, is mediated by dopamine release in the nucleus accumbens. Moreover, the dopamine is released from the reserpine sensitive pool, and probably not from the newly synthesized alpha-MPT-sensitive pool.

Amphetamines↗
PubMed1989

Conditioned stereotypy: behavioral specification of the UCS and pharmacological investigation of the neural change.

Previous work has shown that conditioned stereotypy can be produced by repeated treatments with d-amphetamine or apomorphine. We replicated this phenomenon and found that, as in previous reports, the amplitude of conditioned stereotypy was about one-third that of the unconditioned stereotypy. On the basis of the hypothesis that the UCS in this conditioning situation is a specific stimulation level of dopamine receptors expressed as a peak behavioral effect (UCR), rats were exposed to the experimental boxes for a brief interval during the peak behavioral effect of the drugs. This procedure produced an amplitude of conditioned stereotypy about two-thirds that of unconditioned stereotypy. The issue of the synaptic mechanism mediating conditioned stereotypy was addressed by examining the effect of pimozide on the behavior. A dose of pimozide that completely blocked apomorphine-unconditioned stereotypy also blocked apomorphine-conditioned stereotypy with no sign of motor impairment. d-Amphetamine-conditioned stereotypy was not completely blocked by a dose of pimozide that completely blocked d-amphetamine-unconditioned stereotypy. The implications of these findings for understanding the neural basis of conditioned stereotypy are discussed.

Animals↗
PubMedDate not supplied

Human adipose tissue under in vitro inhibition of 11beta-hydroxysteroid dehydrogenase type 1: differentiation and metabolism changes.

In humans, oxoreducing 11beta-HSD-1 activity appears to be related to body fat distribution in male-type central obesity, but not in female-type peripheral obesity. We postulated that inhibition of 11beta-HSD-1 might have clinical therapeutic significance in oxoreducing mostly visceral fat and its metabolic activity. Our current study investigated the consequence at the cellular level of such inhibition. As an inhibitor of 11beta-HSD-1 activity, we used the licorice derivative carbenoxolone. Carbenoxolone has an inhibitory effect on the activity of both oxidizing 11beta-HSD-2, which converts cortisol to cortisone, and oxoreducing 11beta-HSD-1; yet, preadipocytes and adipocytes only express the latter. Preadipocytes were retrieved from omental and subcutaneous fat from healthy non-obese individuals and differentiated in vitro to mature adipocytes. Activity of 11beta-HSD-1 was assayed by measuring conversion of added 500 nM cortisone to cortisol. Expression of 11beta-HSD-1 mRNA was determined by real-time PCR, while lipolytic effects were determined by measuring glycerol and triglyceride concentration in the culture medium. Carbenoxolone decreased 11beta-HSD-1 activity in a dose-dependent manner with an IC-50 of 5X10 -6 M, but did not affect the expression of 11beta-HSD-1 mRNA. Cortisone stimulated subcutaneous, but not omental preadipocytes proliferation, an effect that was not abolished by carbenoxolone. Dexamethasone had a stimulatory effect on the maturation of both omental and subcutaneous preadipocytes. Carbenoxolone per se, either with or without cortisone, had a negative effect on preadipocyte maturation. Inhibiting 11beta-HSD-1 activity by carbenoxolone had no impact on leptin secretion. Thus, carbenoxolone has no effect on preadipocyte proliferation, but a dramatic inhibitory effect on preadipocyte differentiation into mature adipocytes. The mechanism is only partly related to its inhibitory effect on 11beta-HSD-1 activity. The present observations lend support to the presence of an intracrine loop of a hormone that is both produced from a precursor and active within the preadipocyte and adipocyte.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗