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1. |
Dopamine agonists at repeated “autoreceptor‐selective” doses: Effects upon the sensitivity of A10 dopamine autoreceptors |
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Synapse,
Volume 4,
Issue 4,
1989,
Page 267-280
Michael Jeziorski,
Francis J. White,
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摘要:
AbstractPrevious reports have established the ability of dopamine (DA) agonists to stimulate inhibitory DA autoreceptors at doses which minimally stimulate postsynaptic DA receptors, suggesting that hyperactive DA transmission may be controlled clinically by treatment with DA agonists. Little is known, however, about the possible loss of autoreceptor sensitivity that may occur after repeated treatment with low doses of DA agonists. Extracellular single cell recording and microinotophoretic techniques were used to measure the sensitivity of impulse‐regulating DA autoreceptors on A10 DA cells in the ventral tegmental area (VTA) of chloral hydrate‐anesthetized rats pretreated for seven days with repeated subcutaneous (s.c.) doses of the DA agonist apomorphine (APO). The ability of intravenous (i.v.) administration of the potent D2 DA agonist quinpirole (QUIN) to inhibit the firing of A10 cells was not attenuated in rats pretreated with repeated low doses (2 X 50 μg/kg/day, s.c.) of APO for 7 days, although higher doses (2 X 250 or 500 μg/kg/day) did cause subsensitive responses to QUIN. In rats pretreated with repeated low doses of APO, microiontophoretic application of DA on A10 cells revealed somewhat subsensitive responses. However, ibotenic acid lesions of postsynaptic cells in the nucleus accumbens (NAc) prior to initiation of APO treatment (2 X 50 μg/kg/day) did not alter the response of A10 cells to systemic QUIN, contradicting the possibility that the feedback projection from the NAc to the VTA was compensating for autoreceptor downregulation during systemic challenge with QUIN. In contrast, administration of the irreversible DA antagonist EEDQ (2 mg/kg, i.p.) to control and APO‐treated rats (2 X 50 μg/kg/day) 24 hr prior to recording did reveal a difference in A10 cell sensitivity to systemic QUIN and to microiontophoretic DA between the two groups, suggesting that “spare” DA autoreceptors may have concealed the down‐regulation of autoreceptors induced by repeated low doses of APO. Challenge of A10 DA cells with the partial DA autoreceptor agonist (–)‐3‐(3‐hydroxyphenyl)‐N‐n‐propylpiperidine [(–)3‐PPP], for which an autoreceptor reserve should not exist, produced slightly attenuated responses in APO‐treated rats (2 X 50 μg/kg/day). These findings provide evidence for the existence of spare somatodendritic DA autoreceptors on A10 DA cells with respect to potent DA agonists, suggesting that repeated administration of “autoreceptor‐selective” doses of DA agonists may not result in a dim
ISSN:0887-4476
DOI:10.1002/syn.890040403
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
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2. |
Changes in the structure of synaptic junctions during climbing fiber synaptogenesis |
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Synapse,
Volume 4,
Issue 4,
1989,
Page 281-293
Dennis M. D. Landis,
H. Ross Payne,
Lori A. Weinstein,
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摘要:
AbstractSynaptogenesis between climbing fiber axons and Purkinje cells involves both an orderly translocation of synaptic junctions over the Purkinje cell surface and an elimination of all but one innervating axon. We used thin‐section and freeze‐fracture electron microscopic techniques to study structural changes in synaptic junctions during this interval of synapse translocation and elimination. In freeze‐fractured preparations, virtually all climbing fiber synaptic junctions with the perisomatic processes and somatic spines lacked the particle aggregates that characterized the extracellular half of the postsynaptic membrane of mature synaptic junctions with dendritic spines. Some climbing fiber junctions with the dendritic shaft in the second postnatal week were associated with such aggregates, despite the fact that these junctions are transient. Thus, during the interval when Purkinje cells initially were innervated by multiple climbing fibers, and subsequently denervated of all but one climbing fiber afferent per cell, only a few of the transient synaptic junctions on the cell body and proximal dendrites have associated particles. The presence of a particle aggregate at a synaptic junction does not appear to be correlated with the permanence of that junction and probably is not correlated with the capacity to support synaptic transmission. The particle aggregates might be indicative of relatively long‐lived junctions, or might occur only at junctions formed by the climbing fiber that will persist in synaptic contact with the mature Purkin
ISSN:0887-4476
DOI:10.1002/syn.890040404
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
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3. |
Excitatory amino acid treatment of the ventromedial globus pallidus enhances dopamine utilization in the prefrontal cortex of the rat via the thalamic mediodorsal nucleus |
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Synapse,
Volume 4,
Issue 4,
1989,
Page 294-304
M. W. Jones,
I. C. Kilpatrick,
O. T. Phillipson,
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摘要:
AbstractInfusion of a low dose (5 μM) of the cell‐selective chemical excitant quisqualic acid (QUIS) into rostral ventromedial globus pallidus (GP) had no immediate effect on DA utilization (assessed as [DOPAC]:[DA]and [HVA]:[DA]ratios) in either the medial bank of the prefrontal cortex (FCx) or the agranular insular cortex (AgCx). In contrast, a larger dose (630 μM) of another excitant sodium ibotenate (IBO) produced an immediate bilaterally symmetrical increase in both indices of DA utilization in FCx. There was also a marked trend towards a bilateral increase in these indices of DA utilization in AgCx. In order to determine whether these effects on cortical DA utilization are mediated by a direct cortical route or via the thalamic mediodorsal nucleus (lateral division, MDL), infusions of IBO into GP were repeated in animals with a 1‐week‐old N‐methyl‐D‐aspartate lesion of MDL. The increase in DA utilization of FCx following infusion of IBO into GP was abolished, although the trend towards increased DA utilization in AgCx was still maintained. Since MDLinnervates FCx but not AgCx and since we have previously shown that MDLlesions alone have no effect on DA utilization in either cortical region, the present results suggest that the changes in cortical DA utilization are probably mediated via MD. Thus in addition to the well‐documented control exerted by the thalamus over brain DA function, this has now been extended in the present study to include GP, which projects both directly and indirectly
ISSN:0887-4476
DOI:10.1002/syn.890040405
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
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4. |
Presynaptic cholinergic inhibition in hippocampal cultures |
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Synapse,
Volume 4,
Issue 4,
1989,
Page 305-312
Menahem Segal,
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摘要:
AbstractActivity of hippocampal neurons was recorded in a dissociated culture under patch‐clamp conditions. Excitatory and inhibitory postsynaptic currents (PSCs) were evoked in response to short pulse application of glutamate to other neurons in the culture dish. These PSCs were suppressed by topical application of acetylcholine (ACh) near the recorded neuron. The dose‐dependent effect of the muscarinic antagonist pirenzepine indicates that the effect of ACh is mediated by an M2 receptor. ACh did not affect inward current responses to direct application of glutamate onto postsynaptic neurons. This indicates that ACh may interfere with the release process and not with the postsynaptic response to the neurotransmitter. In some cells, ACh reduced inward Ca currents recorded in the presence of Na and K channel blockers. This effect was atropine sensitive and may underly the reduced PSCs. It is suggested that ACh modulates release of neurotransmitters by reducing presynaptic Ica and thereby reducing evoked P
ISSN:0887-4476
DOI:10.1002/syn.890040406
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
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5. |
Peripheral induction of burst firing in locus coeruleus neurons by nicotine mediated via excitatory amino acids |
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Synapse,
Volume 4,
Issue 4,
1989,
Page 313-318
C.‐S. Tung,
L. Ugedo,
J. Grenhoff,
G. Engberg,
T. H. Svensson,
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摘要:
AbstractThe effect of systemic nicotine administration (50 μg kg−1i.v.) on the activity of brain noradrenaline neurons in the locus coeruleus (LC) of chloral hydrateanesthetized rats was analyzed with single cell recording techniques and quantitative computer assessment of firing rate, degree of bursting, and regularity of firing. Nicotine caused an increased firing rate of the cells, with an average time of onset of 1.7 s. An increase in burst activity was observed, as well as deregularization of the firing pattern. Intraventricularly administered kynurenic acid (1 μmol), an antagonist of excitatory amino acids (EAA), did not change the firing rate of the LC cells, but did induce a marked regularization of their firing pattern into a pacemaker‐like activity and completely abolish burst firing. The EAA antagonist also blocked all of the above effects of nicotine on the LC neurons as well as their typical burst‐activation response to a peripheral, noxious stimulus such as paw‐pinch. Since the circulation time in the rat is about 20 s, these results provide unequivocal evidence for a peripheral site of origin for the rapid LC activation induced by systemic nicotine administration. The data also allow the conclusion that the nicotine‐induced LC activation is indirect and dependent on EAA in brain. Our results provide evidence for a tonically active EAA input to the LC, being of importance for induction of changes in the spontaneous, pacemaker activity of LC neurons into burst firing or more irregular firing patterns. It is suggested that the LC activation by nicotine may be significant in relation to tobacco
ISSN:0887-4476
DOI:10.1002/syn.890040407
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
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6. |
Human cortical neurons contain both nicotinic and muscarinic acetylcholine receptors: An immunocytochemical double‐labeling study |
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Synapse,
Volume 4,
Issue 4,
1989,
Page 319-326
Hannsjörg Schröder,
Karl Zilles,
Paul G. M. Luiten,
Andre D. Strosberg,
Alireza Aghchi,
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摘要:
AbstractUsing immunofluorescence histochemistry, in the human cerebral cortex neurons immunoreactive for both nicotinic and muscarinic acetylcholine receptor proteins could be demonstrated. Vibratome sections of biopsy and autopsy specimens of human temporal and occipital lobes were incubated with monoclonal antibodies specific for muscarinic (M 35) and nicotinic (WF 6) acetylcholine receptor protein. Immunoreactive sites were visualized using a biotin‐streptavidin‐phycoerythrin system (M 35, red fluorescence) and fluorescein‐conjugated immunoglobulins (WF 6, green fluorescence). Immunofluorescence of both antibodies was preponderant in pyramidal neurons located in layers II/III and V and their apical dendrites. Some round and ovoid immunolabeled cells were encountered in layers VI and IV. About 30% of the cholinoceptive cortical neurons, in particular the pyramidal cells, displayed immunoreactivity for both receptor types. The present investigation shows a subpopulation of human cortical neurons to contain both nicotinic and muscarinic receptors. The coexistence of acetylcholine receptors may provide the morphological basis of simultaneous impact of acetylcholine on both receptor types in the same neuron of the human cerebral c
ISSN:0887-4476
DOI:10.1002/syn.890040408
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
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7. |
D1 dopamine receptor stimulation enables the postsynaptic, but not autoreceptor, effects of D2 dopamine agonists in nigrostriatal and mesoaccumbens dopamine systems |
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Synapse,
Volume 4,
Issue 4,
1989,
Page 327-346
Stephen R. Wachtel,
Xiu‐Ti Hu,
Matthew P. Galloway,
Francis J. White,
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摘要:
AbstractPossible functional interactions between D1 and D2 dopamine (DA) receptors were examined using extracellular single‐cell recording with microiontophoretic application of selective D1 and D2 receptor agonists both postsynaptically, in the rat nucleus accumbens (NAc) and caudate‐putamen (CPu), and presynaptically, at impulse‐regulating somatodendritic DA autoreceptors in the ventral tegmental area (A10) and substantia nigra pars compacta (A9) In addition, synthesis‐modulating nerve terminal DA autoreceptors were studied in both the CPu and NAc using the gammabutyrolactone (GBL) neurochemical model of isolated nerve terminal autoreceptor function in vivo.In both the NAc and CPu, the inhibition of neurons produced by iontophoresis of the D2 receptor agonists quinpirole or RU‐24213 was attenuated by acute DA depletion via the tyrosine hydroxylase inhibitor α‐methyl‐p‐tyrosine (AMPT). However, during iontophoresis of the selective D1 DA receptor agonist SKF 38393, the inhibitory effects of the D2 agonists were again evident, suggesting that the attenuation of D2 agonist‐induced inhibition was due to decreased D1 receptor activation. In contrast, the inhibitory effects produced by the non‐selective D1/D2 agonist apomorphine or by SKF 38393 were unaffected by AMPT pretreatment. Thus, D1 receptor activation appears necessary for D2 receptor‐mediated inhibition of NAc and CPu neurons, whereas D2 receptor activation is not required for the inhibition produced by D1 receptor stimulation.In contrast to postsynaptic D2 receptors, the ability of DA agonists to stimulate D2 DA autoreceptors was not altered by manipulations of D1 receptor occupation. Enhancing D1 receptor stimulation with SKF 38393 or reducing D1 receptor occupation with either the selective D1 receptor antagonist SCH 23390 or AMPT failed to alter the rate‐inhibitory effect of i.v. quinpirole on A9 or A10 DA neurons. Similarly, iontophoresis of SKF 38393 failed to alter the inhibitory effects of iontophoretic quinpirole. SKF 38393 also failed to affect the inhibition of GBL‐induced increases in DOPA accumulation (tyrosine hydroxylase activity) produced by quinpirole in either the NAc or CPu. Furthermore, reversal of GBL‐induced increases in DOPA accumulation by apomorphine or quinpirole was unaffected by pretreatment with SCH 23390. Therefore, D1 receptor occupation appears to be necessary for the expression of the functional effects of postsynaptic D2 receptor stimulation but not presynaptic D2
ISSN:0887-4476
DOI:10.1002/syn.890040409
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
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8. |
Autoradiographic quantification of serotonin1Areceptors in rat brain following antidepressant drug treatment |
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Synapse,
Volume 4,
Issue 4,
1989,
Page 347-352
S. A. Welner,
C. De Montigny,
J. Desroches,
P. Desjardins,
B. E. Suranyi‐Cadotte,
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摘要:
AbstractThere is growing evidence that the serotonergic (5‐HT) system is involved in the pathogenesis and treatment of major depression. The 5‐HT receptor subtype involved in the enhancing effect of antidepressant treatments, however, has not been identified. The present study was undertaken to quantify 5‐HT1Asites in the rat brain by autoradiography and membrane binding, using the selective ligand [3H]8‐hydroxy‐N, N‐dipropyl‐2‐aminotetralin (8‐OH‐DPAT), following long‐term antidepressant treatment. Following a 21‐day treatment with amitriptyline (10 mg/kg/day), there was a significant increase of [3H]8‐OH‐DPAT binding measured by autoradiography in the dorsal hippocampus, but there was no change in the nucleus raphe dorsalis; whole brain membrane binding revealed an increase in the number of binding sites, with no change in the affinity for [3H]8‐OH‐DPAT. Conversely, fluoxetine (10 mg/kg/day), a selective blocker of 5‐HT reuptake, and gepirone (10 mg/kg/day), a 5‐HT1Aagonist, both administered for 21 days, significantly reduced [3H]8‐OH‐DPAT binding measured by autoradiography in the nucleus raphe dorsalis without altering hippocampal binding sites. The control active treatment with diazepam (2 mg/kg/day) did not alter [3H]8‐OH‐DPAT binding in the hippocampus or in the nucleus raphe dorsalis. All groups were compared to a 21‐day vehicle‐treated control group. These results are fully consistent with previous electrophysiological and behavioral studies and suggest that alterations of 5‐HT1Areceptors might underlie the enhancement of 5
ISSN:0887-4476
DOI:10.1002/syn.890040410
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
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9. |
Stimulation of d2 dopamine receptors decreases intracellular calcium levels in rat anterior pituitary cells but not striatal synaptosomes: A flow cytometric study using indo‐1 |
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Synapse,
Volume 4,
Issue 4,
1989,
Page 353-370
Marina E. Wolf,
Gregory Kapatos,
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摘要:
AbstractAn important question is whether all D2 dopamine (DA) receptors employ the same signal transduction mechanisms. Anterior pituitary cells and striatal synaptosomes, which possess pharmacologically similar D2 DA receptors, were compared with respect to the effect of D2 DA receptor stimulation on free intracellular Ca2+levels ([Ca2+]i). Flow cytometry, in combination with either the fluorescent calcium indicator indo‐1 or fluorescent voltage‐sensitive dyes, was used to measure [Ca2+]iand to detect changes in membrane potential. In subpopulations of anterior pituitary cells, increases in [Ca2+]iwere produced by elevated K+, veratridine, thyrotropin‐releasing hormone, and BAY K 8644. These increases were blocked by nifedipine, suggesting the involvement of L‐type voltage‐sensitive calcium channels (VSCC's). In 10–15% of the cells, D2 agonists decreased resting [Ca2+]i, reversed stimulus‐induced increases in [Ca2+]i, and caused a hyperpolarization. In striatal synaptosomes, elevated K+and veratridine also increased [Ca2+]i. However, the K+‐induced increase was eliminated if choline was substituted for Na+in the medium, suggesting that Ca2+entry in response to sustained K+depolarization resulted from reversal of Na+/Ca2+exchange. Nifedipine and verapamil inhibited K+‐induced increases in [Ca2+]ionly at concentrations greater than 10 μM, while ω‐conotoxin had no effect. D2 agonists had no effect on resting or stimulated [Ca2+]ibut did hyperpolarize 10–20% of the synaptosomes, indicating that D2 DA receptors are functional in this preparation. The ability of pituitary but not striatal D2 DA receptors to modulate [Ca2+]imay reflect the fact that the two systems differ with respect to
ISSN:0887-4476
DOI:10.1002/syn.890040411
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
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10. |
Mapping cocaine binding sites in human and baboon brain in vivo |
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Synapse,
Volume 4,
Issue 4,
1989,
Page 371-377
Joanna S. Fowler,
Nora D. Volkow,
Alfred P. Wolf,
Stephen L. Dewey,
David J. Schlyer,
Robert R. MacGregor,
Robert Hitzemann,
Jean Logan,
Bernard Bendriem,
S. John Gatley,
David Christman,
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摘要:
AbstractThe first direct measurements of cocaine binding in the brain of normal human volunteers and baboons have been made by using positron emission tomography (PET) and tracer doses of [N‐11C‐methyl]‐(–)‐cocaine ([11C]cocaine). Cocaine's binding and release from brain are rapid with the highest regional uptake of carbon‐11 occurring in the corpus striatum at 4–10 minutes after intravenous injection of labeled cocaine. This was followed by a clearance to half the peak value at about 25 minutes with the overall time course paralleling the previously documented time course of the euphoria experienced after intravenous cocaine administration. Blockade of the dopamine reuptake sites with nomifensine reduced the striatal but not the cerebellar uptake of [11C]cocaine in baboons indicating that cocaine binding is associated with the dopamine reuptake site in the corpus striatum. A comparison of labeled metabolites of cocaine in human and baboon plasma showed that while cocaine is rapidly metabolized in both species, the profile of labeled metabolites is different, with baboon plasma containing significant amounts of labeled carbon dioxide, and human plasma containing no significant labeled carbon dioxide. These studies demonstrate the feasibility of using [11C]cocaine and PET to map binding sites for cocaine in human brain, to monitor its kinetics, and to characterize its binding mechanism by using appropriate pharmacologic
ISSN:0887-4476
DOI:10.1002/syn.890040412
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1989
数据来源: WILEY
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