摘要:

AbstractThe effects of the selective D‐1 dopamine agonist SKF 38893, the selective D‐2 agonist quinpirole, and the nonselective D‐1/D‐2 agonist apomorphine on spontaneous activity of globus pallidus neurons were compared in normal control rats and rats with unilateral 6‐hydroxydopamine induced lesions of the nigrostriatal pathway. In control, unlesioned rats, SKF 38393 (0.4 and 10 mg/kg, i.v.) caused no significant net change in the activity of globus pallidus neurons, although some individual cells showed significant increases of decreases in discharge rates following 10 mg/kg SKF 38393 administration. In animals with unilateral 6‐hydroxydopamine induced lesions, SKF 38393 caused greater increases and decreases in the discharge reates of a larger percentage of pallidal cells recorded on the ipsilateral side than in control, unlesioned animals. These rate changes were effectively reversed by the D‐1 antagonist SCH 23390, but not by the D‐2 antagonist YM‐09151–2. Quinpirole (0.3 mg/kg, i.v.) produced modest rate increases in control, unlesioned animals and significantly larger rate increases in nigrostriatal lesioned animals. YM‐09151–2, but not SCH 23390, effectively reversed quinpirole's effects in the lesioned animals. As previously reported, the nonselective D‐1/D‐2 agonist apomorphine (0.3 mg/kg, i.v.) produced large increases in discharge rates of pallidal cells in control, unlesioned rats. In contrast, in nigrostriatal lesioned rats, the discharge rates of some ipsilateral pallidal neurons were markedly increased, others were decreased, and some were unaffected following apomorphine administration. The dopamine antagonist spiroperidol partially to fully reversed these rate changes. In summary, apomorphine's neurophysiological profile appears to be an exaggeration of the D‐1 agonist profile in the globus pallidus of these lesioned animals. The degree of change observed after apomorphine administration is consistent with results from other studies that have indicated that a synergistic interaction between effects triggered by stimulation of the two receptor subtypes can occur in these animals, as in control, unlesioned animals. However, these results further show that in rats with unilateral nigrostriatal lesions, the denervated dopamine receptors or the processes they mediate are altered so that they no longer have the requirement seen in controls for concurrent stimulation of the complementary dopamine receptor subtype for expression of

ISSN:0887-4476    

DOI:10.1002/syn.890050202

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

年代:1990

数据来源: WILEY

摘要:

AbstractLow magnesium medium and the N‐methyl‐D‐aspartate (NMDA) receptor antagonist D‐2‐amino‐5‐phosphonopentanoate (D‐AP5) were used to analyze the effect of several manipulations on the component of excitatory postsynaptic potentials (EPSPs) mediateed by activation of NDMA receptors in area CA1 of hippocampal slices. The D‐AP5 sensitive component of synaptic response was characterized by a marked sensitivity to changes in extracellular magnesium and calcium concentrations. In both cases the changes in D‐AP5 sensitive responses were considerably larger than those in non‐NMDA‐dependent potentials. Similarly, frequency facilitation, which is due to a transient increase in release, was accompanied by a greater enhancement of NMDA than non‐NMDA receptor‐mediated components. The degree of paired‐pulse facilitation observed with D‐AP5 sensitive responses was magnesium‐dependent between, concentrations of 0.05 and 0.5 mM, an effect not seen with control potentials. Intracellular injections of hyperpolarizing current pulses differentially affected NMDA and non‐NMDA receptor‐mediated components. Taken together, these results indicate that changes in the amount of transmitter release may affect to agreater degree NMDA than non‐NMDA receptor‐mediated components of synaptic responses, probably because of the voltage‐sensitive blockade by magnesium of the NMDA receptors. In contrast, induction of long‐term potentiation (LTP) by high frequency stimulation produced a larger increase in non‐NMDA as opposed to NMDA receptor‐dependent responses, a result that does not support the idea that an increa

ISSN:0887-4476    

DOI:10.1002/syn.890050203

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

年代:1990

数据来源: WILEY

摘要:

Abstract1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) is a potent dopaminergic toxin that has been found to produce Parkinson's disease‐like symptoms in humans and monkeys. The neurotoxic effects of MPTP appear to be reduced in rodents where multiple dosing procedures are required to demonstrate long‐lasting neuronal deficits. In the present study, the neurotoxic effects of MPTP were further characterized in the rat. Following the repeated administration of MPTP, pronounced (60–80%) and dose‐dependent depletions of striatal dopamine and serotonin concentrations were found in the rat brain. Time‐course studies revealed that while striatal dopamine concentrations remained consistently reduced for at least 8 weeks following MPTP treatment, striatal serotonin depletions as well as MPTP‐induced monoamine depletions in other brain regions were transient in nature. Pretreatment with the MAO‐B inhibitor pargyline afforded a selective and complete protection of striatal dopamine levels without significantly affecting MPTP‐induced striatal serotonin depletions. Similarly, treatment with ascorbic acid was found to selectively attenuate MPTP‐induced dopamine depletions in rats. The neurotoxic effects of MPTP were also found to increase in the developing rat. No significant brain monoamine depletions were observed in neonatal rats following the repeated administration of MPTP. However, MPTP‐induced neurotoxicity progressively increased in older rats. The present results indicate that when appropriate treatment procedures are used, a pronounced, selective, age‐dependent, and long‐lasting MPTP‐induced reduction in striatal dopamine concentrations can be observed in the rat brain. The present results are discussed in references to the putative mechanisms and species differ

ISSN:0887-4476    

DOI:10.1002/syn.890050204

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe involvement of dopamine (DA) in human and experimental epilepsy has been discounted as DAergic drugs have little effect on convulsions. This work presents evidence that bilateral microinjection of the DA D1agonist SKF‐38393 into the substantia nigra enhances the susceptibility of rats to seizures, with and ED50fo 20 pmol (range 13‐31 pmol), converting subconvulsant doses of the cholinergic agonist pilocarpine (200 mg/kg; i.p.) into convulsant ones. The proconvulsant action of SKF‐38393 was reversed by blocking D1‐mediated transmission in the substantia nigra with the D1antagonist SCH‐23390. The D2agonist LY‐171555 did not modulate the threshold for limbic seizures when injected into the substantia nigra. In the striatum, the D2agonist LY‐171555 protected rats against limbic seizures induced by systemic administration of pilocarpine (380 mg/kg; i.p.), with an ED50of 2 pmol (range 1.4–2.8 pmol). The anticonvulsant action of LY‐171555 in the striatum was reversed by haloperidol. The D1agonist SKF‐38393 did not affect pilocarpine seizures following administration into the striatum. Systemic administration of DAergic drugs showed that the D1agonist SKF‐38393 decreased the threshold for pilocarpine seizures, with an ED50of 0.81 mg/kg (range 0.45–1.47 mg/kg), whereas the D2agonist LY‐171555 had no effect on susceptibility of rats to pilocarpine. Thr proconvulsant action of SKF‐38393 was blocked by the D1antagonist SCH‐23390. These results suggest that DA differentially modulates seizure threshold in the forbrain acting via D1mechanisms in the substantia nigra and

ISSN:0887-4476    

DOI:10.1002/syn.890050205

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe dorsal and median raphe 5‐HT neurons give rise to projections that differ in axon morphology and in vulnerability to certain amphetamine derivatives. The present study was undertaken to determin if these two 5‐HT systems possess different functional properties. To this end, we studied the effects of selective 5HT1Aor 5‐HT1A/5‐HT1Breceptor agonists and ofp‐chloroamphetamine on extracellular levels of indoleamines, as measured by differential pulse voltammetry with electrochemically pretreated carbon fiber electrodes, in cell body and nerve terminal regions of these subsets of 5‐HT neurons in the rat brain. The selective 5‐HT1Aagonist 8‐OH‐DPAT produced a gradual decrease in the height of 300mV oxidation peak in the dorsal raphe and in the frontal cortex, reaching a maximum of 60% 3 h after the i.v. injection of 30 m̈g/kg. However, the same dose of 8‐OH‐DPAT was ineffective in the median raphe and in the dentate gyrus that receives its 5‐HT innervation exclusively from the median raphe. A higher dose of 8‐OH‐DPAT (150 m̈g/kg, i.v.) produced a 60% decrease in the height of the 300 mV oxidation peak in the median raphe, whereas only a 20% decrease was obtained in the dentate gyrus. In contrast, the non‐selective 5‐HT1agonist RU 24 969 (10 mg/kg, i.p.) caused 70% reduction of the 300 mV peak height in both the dorsal and median raphe and a 50% decrease in both the frontal cortex and the dentate gyrus. Moreover, although a high dose of 8‐OH‐DPAT (150 m̈g/kg, i.v.) given alone reduced by 20% the amplitude of the oxidative peak in the dentate gyrus, subsequent administration of RU 24 969 (10 mg/kg, i.p.) caused a further 30% diminution of the oxidative peak height. The greater responsiveness of dorsal as compared to median raphe 5‐HT systems to 5‐HT1Areceptor agonists was confirmed in two further series of experiments. First, the microiontophoretic application of 8‐OH‐DPAT directly onto 5‐HT neurons was three times more potent in suppressing the firing rate of dorsal raphe 5HT neurons than that of their median raphe congeners. Second, 8‐OH‐DPAT and buspirone were ten and four times, respectively, more potent in decreasing 5‐HT skynthesis in the frontal cortex than in the hippocampus. Three hours after the administration ofp‐chloroamphetamine (5 mg/kg, i.p.), the height of the 300 mV peak was increased by 60% in the frontal cortex but was unchanged in the dentate gyrus. The following conclusions can be drawn from the present investigation: (1) the dorsal raphe‐frontal cortex 5‐HT system exhibits a greater responsiveness of a 5‐HT1Aagonist than does the median raphe‐dentate gyrus 5‐HT system; (2) in the latter system, 5‐HT1Areceptor activation caused a greater reduction in extracellular indoleamines at the level of the cell bodies than in the corresponding terminal fields (dentate gyrus); (3) the terminal 5‐HT1Bautoreceptor seems to play a more important role in the control of 5‐HT release in the dentate gyrus than in the frontal cortex; and (4) 5‐HT terminals in the dentate gyrus appear to be insensitive to the 5‐HT‐releasing effect ofp‐chloramphetamine, which is consistent with

ISSN:0887-4476    

DOI:10.1002/syn.890050206

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe Akaike information criterion (AIC) and other criteria that trade off the goodness‐of‐fit against the number of parameters have been used to determine the number of ion channel states from single channel recordings. We show that, in general, such criteria are not valid. This is illustrated by an elementary example in which the AIC yields an incorrect result. The implications of these findings for the discrimination of different kinetic models of ion channels are discus

ISSN:0887-4476    

DOI:10.1002/syn.890050207

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

年代:1990

数据来源: WILEY

摘要:

AbstractThis report evaluates two morphological markers of synaptogenesis following the induction of long‐term potentiation (LTP) in the dentate gyrus of the anesthetized rat. These two morphological features, polyribosomes and multiple synaptic contacts, are known to increase in number with synaptogenesis in the mature hippocampus.The analysis focused on the middle third of the dentate molecular layer. As shown previously, this is the region of primary synaptic activation in our electrophysiological protocol and the region of localized morphological changes with LTP. Here the incidence of a polyribosome at the base of a dendritic spine declined 57% with LTP. In addition, the number of multiple synaptic contacts decreased 18% there with LTP. Both decreases were more pronounced immediately following conditioning stimulation than at later intervals. Beacause both morphological features decrease with LTP but increase with synaptogenesis, the data do not support the hypothesis that new synapses form with LTP. Instead, the data add further support to the view that the strengthening of existing excitatory synapses underlines LT

ISSN:0887-4476    

DOI:10.1002/syn.890050208

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

年代:1990

数据来源: WILEY

摘要:

AbstractVisceral afferent neurons of the nodose and petrosal ganglia are immunoreactive (ir) for many neurotransmitters [e.g., substance P (SP), neurokinin A (NKA), calcitonin gene‐related peptide (CGRP), and dopamine (tyrosine hydroxylase‐ir; TH)]. Coexistence of SP‐ir with NKA‐, CGRP‐, or TH‐ir was studied in individual neurons of the rat ganglia using fluorescene immunocytochemistry. SP‐ and NKA‐ir were present in equal numbers of cells and were consistently colocalized. SP‐ and CGRP‐ir were found to be similarly distributed in scattered cells, concentrated mostly in the rostral pole of the nodose ganglion and in the petrosal ganglion. SP‐ir completely coexisted with CGRP‐ir. However, there was at least twice the number of CGRP‐ir neurons as SP‐ir neurons, and thus CGRP‐ir neurons that did not contain SP‐ir were also present. In contrast, SP‐ and TH‐ir had different distributions in both the nodose and the petrosal ganglia. SP‐ir was located in the more rostral regions of both the nodose and petrosal ganglia, whereas TH‐ir was detected throughout the entire nodose ganglion and only in the most caudal region of the petrosal ganglion. There was no coexistence of SP‐ and TH‐ir. These data demonstrate the differential localization and coexistence of putative transmitters in visceral sensory

ISSN:0887-4476    

DOI:10.1002/syn.890050209

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe levels of serotonin (5‐HT), 5 hydroxyindoleacetic acid (5‐HIAA), dopamine (DA), homovanillic acid (HVA), norepinephrine (NE), and tyrosine hydroxylase (TH) activity were measured in the focus (spiking) and nonfocus (nonspking) regions of the temporal neocortex of 20 patients with intractable complex partial seizures. The levels of 5‐HT, DA, 5‐HIAA, and HVA were higher in the focus when compared to the nonfocus. Values for NE and TH activity were not different when focus and nonfocus were compared. The ratios of metabolite to precursor for 5‐HT and DA were not significantly different between the focus and the nonfocus, suggesting that the changes observed were the result of a modification in the synthesis and release of these amines. Such changes in the epileptic focus could be caused by altered transsynaptic regulatory processes, which occur as a result of neuronal loss, gliosis, or neuronal

ISSN:0887-4476    

DOI:10.1002/syn.890050210

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe nigrostriatal dopamine (DA) system is sexually dimorphic. In female but not male rats, striatal DA activity is modulated by gonadal steroid hormones. Ovariectomy (OVX) decreases striatal DA release and turnover. Estrogen replacement restores the response to that of the intact female in estrus. In contrast, castration (CAST) of male rats has no effect on the stimulated release of DA from striatal tissue. This report addresses the question: Dose estrogen act directly on the striatum to induce changes in DA release? Physiological concentrations of 17b̃‐estradiol and other steroids or a nonsteroidal estrogen analog were applied directly to striatal tissue maintained in an in vitro superfusion system. The effect of hormonal treatments on the responsiveness of striatal DA terminals to stimulation was examined in tissue from OVX females and intact and CAST male rats. The results are summarized as follows: (1) Infusion of 17b̃‐estradiol (p<0.01) and diethylstilbesterol (p<0.05) increased amphetamine (AMPH)‐stimulated striatal DA release from striatal tissue of OVX female rats compared with the effect of cholesterol. 17alpha‐Estradiol also tended to potentiate the striatal DA response to AMPH, but this result was not statistically significant (p<0.062). 17b̃‐Estradiol had no effect on AMPH‐stimulated DA release from striatal tissue of intact male rats. (2) The KCl‐stimulated release of DA from striatal tissue of OVX rats exposed in vitro to 100 pg/ml 17b̃‐estradiol (a physiological dose) was significantly greater (p<0.05) than the response after exposure to vehicle. In contrast, 1,000 pg/ml 17b̃‐estradiol produced a decrease in KCl‐induced striatal DA release (p<0.05), whereas 17alpha‐estradiol (100 pg/ml or 1,000 pg/ml) did not significantly influences the response to KCl. (3) The pulsatile administration of 17b̃‐estradiol stimulated DA release from strital tissue of OVX females (p<0.05; compared with tissue from an OVX group that received vehicle or CAST male rats exposed to either 17b̃‐estradiol or vehicle). It is concluded that with tissue from OVX rats, physiological concentrations of estrogen can act directly on striatal tissue in vitro to stimulate DA release and to increase striatal DA responsiveness to stimulation, whereas prolonged exposure or high concentrations of 17b̃‐estradiol decreases striatal DA responsiveness. The striatum and/or the striatal DA system ar

ISSN:0887-4476    

DOI:10.1002/syn.890050211

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

年代:1990

数据来源: WILEY