摘要:

AbstractThe influence of spontaneous muscle activity on acetylcholine receptor (AChR) expression was examined by exposing long‐term cultures of mammalian myotubes to two pharmacological agents that have similar effects on the rate of spontaneous contractile activity but pharmacologically distinct actions on voltage gated Na+channels. Previous studies by other investigators have shown that tetrodotoxin upregulates and that veratridine downregulates surface AChR expression in short‐term mammalian muscle cultures. In order to determine whether these drugs have disparate actions on AChR mRNA levels, myotubes were exposed to either tetrodotoxin or veratridine for a period of 10 days, and measurements of the relative levels of embryonic AChR subunit mRNAs (alpha, beta, gamma, delta) were obtained during and following the period of drug exposure. Veratridine produced a substantial decrease (between 33% and 50% reduction), while tetrodotoxin produced a relatively small increase (between 17% and 23%), in each of the AChR subunit mRNAs after 6 days of drug exposure. At 23 days in culture, spontaneously active myotubes exhibited a decrease in the relative levels of each of the AChR subunit mRNAs. Myotubes previously exposed to either veratridine or tetrodotoxin exhibited elevated levels of beta, gamma, and delta AChR subunit mRNAs 6 days after cessation of drug treatment, thus suggesting that a period of muscle inactivity can induce sustained influences on some AChR mRNA levels. These results indicate that the disparate effects of veratridine and tetrodotoxin on surface AChR expression are partly mediated by opposing alterations in AChR subunit mRNA levels, and suggest that changes in the resting influx of sodium and/or calcium ions that are independent of spontaneous electrical or contractile activity can modulate intracellular levels of AChR subunit mRNAs. © 1994 Wiley‐Lis

ISSN:0887-4476    

DOI:10.1002/syn.890180402

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractIn rats with a unilateral 6‐hydroxydopamine lesion of the dopaminergic nigro‐striatal pathway, striatal Dl‐receptor‐stimulated c‐fos expression and turning behavior are positively modulated by D2receptor stimulation and by blockade of N‐methyl‐D‐aspartate (NMDA) or muscarinic receptors. Combined D1/D2receptor stimulation by L‐dopa activates c‐fos in a manner not additive with muscarinic receptor blockade by scopolamine. On the other hand, blockade of NMDA receptors by MK 801 reduced c‐fos expression induced by L‐dopa while, depending on the dose of L‐dopa, differentially affecting contralateral turning behavior. The results are interpreted to suggest that D2receptor stimulation amplifies D1‐receptor‐mediated c‐fos expression by two mechanisms differentially related to muscarinic and NMDA r

ISSN:0887-4476    

DOI:10.1002/syn.890180403

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractIn vivo brain microdialysis was used to determine the effects of the standard tricyclic antidepressant imipramine and the two selective serotonin reuptake inhibitors (SSRIs) antidepressants, fluoxetine and fluvoxamine, on extracellular levels of norepinephrine (NE), dopamine (DA), and serotonin (5‐HT) in rat medial prefrontal cortex. When given intraperitoneally (IP), imipramine increased NE in the microdialysis perfusate, and elevated DA and 5‐HT to a lesser extent. Similar dose‐dependent increases in DA and 5‐HT were detected after IP fluoxetine, although NE was less affected. In contrast, IP fluvoxamine produced no change in basal NE nor DA, although a large increase in 5‐HT occurred at an intermediate dose. When administered directly into cortex, all three antidepressants increased 5‐HT by the same amount in a dose‐dependent fashion. Intracortical imipramine and fluoxetine increased NE, and fluoxetine and fluvoxamine both increased DA, with fluoxetine doing so at a lower concentration. These data suggest that the SSRIs are not entirely selective for serotonin in vivo. © 1994 W

ISSN:0887-4476    

DOI:10.1002/syn.890180404

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractMechanisms for the induction and expression of long‐term potentiation (LTP) were studied in slices of piriform cortex. Cooperativity among afferent inputs as a controlling factor for induction of LTP was tested by pairing stimulation of one input that normally does not induce LTP with stimulation of another input. Combined stimulation, given either to two weak inputs with simultaneous bursts or by pairing single pulses with bursts, did effectively induce LTP. Tests for expression of LTP by NMDA vs. non‐NMDA receptors indicated that non‐NMDA receptor‐mediated responses expressed much greater LTP than NMDA receptor‐mediated responses. Ratios for paired‐pulse facilitation and depression were not altered after induction of LTP. These characteristics are comparable to those exhibited by synapses in the CA1 field of hippocampus. © 1994 Wil

ISSN:0887-4476    

DOI:10.1002/syn.890180405

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe effect of morphine on serotonin (5‐HT) was examined by microdialysis in unanesthetized and anesthetized rats. In unanesthetized rats, morphine (10 mg/kg, s. c.) produced increases in extracellular 5‐HT in nucleus accumbens (n. accumbens) and dorsal raphe nucleus (DRN), but not in the dorsal hippocampus. Similarly, extracellular 5‐HT in the n. accumbens, but not the dorsal hippocampus, was increased after morphine (1 μM) was infused for 60 min by reverse dialysis into the DRN. Chloral hydrate, pentobarbital, and ketamine anesthesia had different effects on 5‐HT in the n. accumbens. Chloral hydrate induced a transient increase and ketamine a sustained increase in extracellular 5‐HT. Pentobarbital caused a sustained decrease. The effects of systemic and intraraphe administration of morphine were abolished by all three anesthetics. Infusion of muscimol, a GABAAreceptor agonist, into the DRN also induced a decrease in 5‐HT and abolished the effects of morphine on 5‐HT in the DRN and n. accumbens. These results are consistent with other evidence suggesting that morphineinduced increases in monoamine neurotransmission are a disinhibitory effect resulting from opioid‐mediated inhibition of GABA release. More conclusively, it is apparent that anesthetized animals are inappropriate for testing the effect of morphine on 5‐HT neurotransmission. © 1

ISSN:0887-4476    

DOI:10.1002/syn.890180406

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractWe utilized quantitative autoradiography to determine the distribution of receptors for thyrotropin‐releasing hormone (TRH) throughout the human temporal lobe and to examine the distribution of these receptors in discrete subregions of the temporal lobe from patients diagnosed premortem with schizophrenia. When compared to non‐neurologic controls, schizophrenic patients demonstrated an increase of 51% in the concentration of TRH receptors in the molecular layer of the dentate gyrus. Within nuclei of the schizophrenic amygdala, marked decreases were found in the central (44%), medial (38%), cortical (36%), accessory cortical (52%), lateral (54%), and medial basal (22%) nuclei. We also examined postmortem brain samples from patients with Huntington's disease, amyotrophic lateral sclerosis, and Alzheimer's disease for alterations in the distribution of TRH receptors. No significant differences from non‐neuropsychiatric controls were noted within the hippocampus in any of these disease states; however, slight alterations were noted in the central and medial basal amygdala in Huntington's disease and in the cortical amygdala in Alzheimer's disease. These disease‐specific findings suggest that TRH may play a role in the neurochemical dysfunction of schizophrenia. © 1994 Wiley

ISSN:0887-4476    

DOI:10.1002/syn.890180407

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe cellular mechanisms underlying the effects of high pressure, GABAergic presynaptic inhibition, and low [Ca2+]0on glutamatergic excitatory synaptic transmission were studied in the opener muscle of the lobster walking leg. Excitatory postsynaptic currents (EPSCs) were recorded with or without prior stimulation of the inhibitor using a loose macropatch clamp technique at atmospheric pressure and at 6.9 MPA helium pressure. High pressure reduced the mean EPSC amplitude and variance, decreased the quantal content (m), but did not affect the quantum current (q). Pressure shifted the median of the amplitude histogram to the left by 1–2 q. Under normal pressure conditions, presynaptic inhibition and low [Ca2+]0induced similar effects. However, quantal analysis using a binomial frequency distribution model revealed that high pressure and low [Ca2+]0diminished n (available active zones) and slightly increased p (probability of release), but presynaptic inhibition reduced p and slightly increased n. At high pressure, presynaptic inhibition was reduced, at which time the major contributor to the inhibitory process appeared to be reduction in n and not p. The similarity of the alterations in quantal parameters of release at high pressure, low [Ca2+]0, and in some conditions of presynaptic inhibition is consistent with the hypothesis that pressure reduces Ca2+inflow into the presynaptic nerve terminals to affect the Ca2+‐dependent quantal release parameters n and p. © 1994 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of A

ISSN:0887-4476    

DOI:10.1002/syn.890180408

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractPrevious in vivo studies reporting a dose‐dependent increase in extracellular dopamine (DA) levels by excitatory amino acid (EAA) antagonists have been interpreted to indicate a lack of tonic excitatory effect exerted by these amino acids on striatal DA release. Alternatively, a tonic excitatory influence on DA release may affect a small fraction of DA terminals, so that blockade of this effect does not make a great enough contribution to the extracellular fluid to be detected by microdialysis. To examine this possibility, the effect of EAA antagonists was assessed by microdialysis in the presence of DA uptake blockers. It was found that in the presence of nomifensine or cocaine, antagonists of either NMDA or AMPA/kainate receptors decreased extracellular DA levels in the striatum. These data suggest that EAAs may exert a tonic facilitatory influence on striatal DA release and/or that endogenous EAAs may potentiate the action of DA uptake blockers through mechanisms that are mediated by EAA receptors. © 1994 Wiley‐Liss,

ISSN:0887-4476    

DOI:10.1002/syn.890180409

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe role of N‐methyl‐D‐aspartate (NMDA) excitatory amino acid receptors in D‐amphetamine (AMPH)‐induced behavioral changes and increased expression of the nuclear transcription factors, c‐fosandzif/268, and preprodynorphin (PPD) mRNA in various regions of rat forebrain was investigated with quantitative in situ hybridization histochemistry. Three hours after a single injection of AMPH (5 mg/kg, i.p.), the mRNA expression ofzif/268, but not c‐fos, in dorsal striatum (caudate nucleus) and cerebral cortex (sensorimotor cortex), and PPD mRNA in dorsal striatum, was upregulated. Pretreatment of rats with MK‐801 (0.5 mg/kg, i.p.) attenuated AMPH‐induced striatal and cortical expression ofzif/268mRNA and striatal expression of PPD mRNA, without affecting the behavioral alterations induced by AMPH. A similar, dose‐dependent suppression of AMPH‐inducedzif/268and PPD mRNA in striatum and cortex was also revealed after systemic administration of (±)‐3‐(2‐carboxypiperazin‐4‐yl)‐propyl‐l‐phosphonic acid (CPP) at doses of 5 and 10 mg/kg. CPP, only at the higher dose, slightly attenuated behavioral activity induced by AMPH. MK‐801 and CPP (at higher dose) alone suppressed basal (constitutive)zif/268mRNA levels in both striatum and cortex regions. No significant effect of either antagonist was found on constitutive expression of striatal PPD mRNA. These studies indicate that NMDA receptors mediate, at least in part, activation ofzif/268and PPD gene expression in striatum and sensorimotor cortex by a single injection of AMPH. Furthermore, NMDA receptor‐mediated gene regulation more likely is involved in long‐term neuronal plasticity to drug exposure than in acute drug effects since NMDA receptor antagonists had little or no effect on the acute behavi

ISSN:0887-4476    

DOI:10.1002/syn.890180410

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractInterleukin‐1 (IL1) is a key messenger implicated in endocrine and immune systems that interact to mediate the stress response. Corticotropin‐releasing factor (CRF) secretion and synthesis in the NPLC‐KC human hepatoma cell line has been shown to respond to IL1 stimulation. We have studied how various inhibitors of second messenger pathways alter this IL1 effect. NPLC‐KC cells were grown in six‐well Costar plates and treated for 12 or 24 h with or without 500 pM IL1 (α form) in the presence of various inhibitors of second messenger pathways. Inhibitors included the protein kinase C (PKC) inhibitor, H‐7; the protein kinase A inhibitor, IP20; or the cyclooxygenase inhibitor indomethacin (IND). Both cell extracts and secretion media were assayed for CRF‐like immunoreactivity by radioimmunoassay. IP20, H‐7, and IND all reduced basal CRF secretion at 24 h but not at 12 h. No effects were seen on basal CRF synthesis with these inhibitors. The three inhibitors also reduced ILl effects on CRF secretion at 12 and 24 h. The reduction seen with all three inhibitors was statistically significant (P<0.05) at 12 h. Although a reduction was seen with all three inhibitors at 24 h, a statistically significant reduction (P<0.05) was demonstrable only for H‐7. IL1 stimulated CRF synthesis in the NPLC‐KC cells appears to only involve PKC pathways. Only the PKC inhibitor H‐7 reduced the augmentation that IL1 produces on CRF synthesis. This effect was statistically significant at 12 and 24 h (P<0.05).

ISSN:0887-4476    

DOI:10.1002/syn.890180411

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY