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1. |
PET examination of the monoamine transporter with [11c]β‐CIT and [11c]β‐CFT in early parkinson's disease |
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Synapse,
Volume 21,
Issue 2,
1995,
Page 97-103
Juha O. Rinne,
Arto Laihinen,
Kjell Någren,
Hanna Ruottinen,
Ulla Ruotsawnen,
Urpo K. Rinne,
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摘要:
AbstractThe monoamine transporter was studied in 4 healthy controls and 5 patients with early Parkinson's disease (PD), who had not received any antiparkinsonian medication, by means of positron emission tomography (PET) using two novel ligands, [11C]β‐CIT and [11C]β‐CFT. Both ligands showed highest uptake in the striatum. There was intermediate accumulation of activity in the thalamus and midbrain, which was more marked for [11C]β‐CIT than for [11C]β‐CFT. In the cortical areas, uptake of both ligands was not different from that seen in the cerebellum. In the controls, the putamen‐to‐cerebellum and caudate‐to‐cerebellum ratios for [11C]β‐CFT were higher than those for [11C]β‐CIT (putamen: 3.15± 0.39 for [11C]β‐CFT, and 1.84 ±0.10 for [11C]CIP‐CIT caudate: 3.15±0.31 for [llC]P‐CFT, and 1.95±0.17 for [11C]β‐CIT). Reduction from mean control value in PD patients was greater for [11C]β‐CFT (45% in the putamen contralateral to the predominant symptoms,P0.05). [11C]β‐CFT uptake in the caudate nucleus was also diminished in PD patients (to 80% of the control mean,P<0.05), whereas [11C]β‐CIT was within normal range (reduced to 90% of the control mean). These results indicate that both [11C]β‐CIT and [11C]β‐CFT are useful PET ligands to study brain monoamine transporter in healthy controls and in patients with PD. However, [11C]β‐CFT seems su
ISSN:0887-4476
DOI:10.1002/syn.890210202
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1995
数据来源: WILEY
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2. |
Plastic effect of soiled bedding on the structure of synapses in rat accessory olfactory bulb |
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Synapse,
Volume 21,
Issue 2,
1995,
Page 104-109
Masumi Ichikawa,
Masato Matsuoka,
Yuji Mori,
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摘要:
AbstractThe effects of exposure to soiled bedding on synaptic morphology in the accessory olfactory bulb (AOB) were examined in adult male rats. Forty‐day‐old male rats were isolated. One group was exposed to bedding soiled by male and female rats (EC). Another group was exposed only to male‐soiled bedding (SC). A third group was exposed to clean bedding (IC). After 2 months, the animals were sacrificed for electron microscopy. The size and the numerical density of synapses were measured in the glomerulus and the granule cell layer. In the glomerulus, the mean size of the synapses was significantly greater in the EC than in the IC group, whereas that in the SC group appeared to be intermediate between those in the EC and the IC groups but was not significantly different from those in the EC and the IC groups. There was no statistically significant difference in the density of synapses among the three groups. Synapses in the granule cell layer are classified into two types: (1) perforated synapses, which are characterized by discontinuities in their postsynaptic thickenings, and (2) nonperforated synapses. The mean size of perforated synapses was significantly greater in the EC than in the IC and SC groups; however, no statistically significant difference was observed in the size of nonperforated synapses among the three groups. Moreover, no statistically significant difference was observed in the numerical densities of either perforated or nonperforated synapses among the three groups. These results suggested that exposure to a more complex soiled bedding environment (i.e., to bedding soiled by both male and female rats) can induce greater structural changes of the synapses in the AoB of male adult rats. © 1995 Wiley‐L
ISSN:0887-4476
DOI:10.1002/syn.890210203
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1995
数据来源: WILEY
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3. |
Electrochemical evidence of increased dopamine transmission in prefkontal cortex and nucleus accumbens elicited by ventral tegmental μ‐opioid receptor activation in freely behaving rats |
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Synapse,
Volume 21,
Issue 2,
1995,
Page 110-122
Miriam Beth Noel,
Alain Gratton,
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摘要:
AbstractChronoamperometry was used in combination with monoamine‐selective electrodes to monitor, in nucleus accumbens (NAcc) and prefrontal cortex (PFC) of freely behaving rats, changes in dopamine (DA)‐like electrochemical signals elicited by unilateral ventral tegmental microinjections of the selective μ‐opioid receptor agonist D‐Ma, N‐Me‐Phe‐Gly‐01‐Enkephalin (DAMGO; 0.01, 0.1, and 1.0 nmol). The results show that DAMGO dose‐dependently increased electrochemical signals both in NAcc and PFC within a few minutes of injection. While DAMGO elicited signal increases of comparable amplitudes in both regions, the increases recorded in PFC were significantly longer lasting than those in NAcc; at the highest dose tested (1.0 nmol), DAMGO produced signal increases that lasted (mean ± sem) 129 ± 7.3 min in PFC and 96 ± 12.5 min in NAcc. Pretreatment with the opioid receptor antagonist, naloxone (2 mgkg, sc), significantly attenuated the peak amplitude and reduced the duration of DAMGO‐in‐ duced (0.1 nmol) signal increases both in PFC and NAcc. In contrast, pretreatment with apomorphine (50 μg/kg, sc), a D1/D2 DA receptor agonist, significantly reduced the duration and the rate of rise of the signal increases in both regions but had little effect on the peak increases in signal. Unilateral ventral tegmental DAMGO administration (0.01, 0.1, and 1.0 nmol) also caused dose‐dependent increases in contraversive circling the duration of which approximated that of the signal increases recorded in NAcc. However, differences in the time courses of DAMGO‐induced contraversive circling and signal increases in NAcc suggest that the behavioral stimulant effect of ventral tegmental μ‐opioid receptor activation may not be mediated exclusively by meso‐NAcc DA neurons. The results of this study suggest that enkephalins modulate the activity of meso‐PFC DA neurons and that behaviorally relevant activation of μ‐opioid receptors in the ventral tegmental area increases DA transmission in PFC to a same, if not to a greater extent as in NAcc. These findings are discussed in relation to evidence indicating that the response of meso‐NAcc DA neurons to a variety of stimuli, including drugs of abuse, is indirectly regulated by a DA‐se
ISSN:0887-4476
DOI:10.1002/syn.890210204
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1995
数据来源: WILEY
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4. |
Protein kinase C inhibitors enhance the 5‐HT2Areceptor‐mediated excitatory effects of serotonin on interneurons in rat piriform cortex |
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Synapse,
Volume 21,
Issue 2,
1995,
Page 123-130
Gerard J. Marek,
George K. Aghajanian,
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摘要:
AbstractPreviously it has been shown that excitatory effects of 5‐hydroxytryptamine (5‐HT) upon interneurons in the rat piriform cortex are mediated by 5‐HT2Areceptors. This receptor is linked to phosphoinositide turnover, and one consequence of stimulating this receptor is the activation of protein kinase C (PKC). In the present study, the effect of PKC inhibitors on the 5‐HT excitation of piriform cortical interneurons was examined by extracellular recording in a rat brain slice preparation. Bath application of the selective PKC inhibitors, bisindolylmalemide and chelerythrine, and the nonselective protein kinase inhibitor, H‐7, all enhanced the excitatory effects of 5‐HT. Two other nonselective protein kinase inhibitors, H‐8 and HA 1004, which are 2.5‐fold and 6.7‐ fold less potent than H‐7 at inhibiting PKC, produced a slight or no enhancement, respectively, of the excitatory effect of 5‐HT. Bisindolylmalemide, chelerythrine, and H‐7 did not enhance the excitatory effects of norepinephrine or carbachol on the same interneurons. The PKC activator phorboll2,13‐diacetate (PDA) decreased the excitatory effect of 5‐HT this decrease was rapidly reversed by H‐7. As inhibitors of PKC selectively enhanced rather than blocked the excitation by 5‐HT mediated by 5‐HT2Areceptors, we conclude that activation of PKC does not mediate the excitation by 5‐HT of piriform cortical interneurons. Instead, we propose that PKC may have a negative feedback role in modulating the excitation by 5‐HT of piriform cortical
ISSN:0887-4476
DOI:10.1002/syn.890210205
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1995
数据来源: WILEY
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5. |
Evaluation of three transporter ligands as quantitative markers of serotonin innervation density in rat brain |
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Synapse,
Volume 21,
Issue 2,
1995,
Page 131-139
Laurent Descarries,
Jean‐Paul Soucy,
Francine Laeaille,
Abdelghani Mrini,
Richard Tanguay,
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摘要:
AbstractDirect counting of axon terminals (varicosities) labeled by uptake/storage of a tritiated monoamine provides a means to test radioligands of the corresponding membrane transporter as quantitative markers of regional monoamine innervation density in brain tissue. In autoradiographs from alternate rat brain slices, counts of [3H]5‐HT‐ labeled axon terminals were matched with densitometric measurements of the specific binding of tritiated cyanoimipramine (CYI), citalopram (CITAL), and 6‐nitroquipazine (6‐ NTQ), under conditions of hypo‐, normo‐, or hyper‐5‐HT innervation of the neostriatum. A total of 267 pairs of data were subjected to a multilevel analysis (iterative generalized least square procedure). With all three ligands, there was a linear relationship between the density of 5‐HT innervation and the density of specific binding and no change in the slope of the regression lines as a function of 5‐HT innervation density. Thus, none of these ligands gave any sign of down‐ or up‐regulation of the 5‐HT transporter consequent to 5‐HT hypo‐ or hyper‐innervation. The regression lines for CYI and CITAL were not significantly different from one another and crossed the ordinate near zero, whereas the regression line for 6‐NTQ was less steep and had a higher intercept with the ordinate. In addition, the dispersion of values around the regression line (residuals) was lower with CYI and CITAL than 6‐NTQ. It was concluded that both CYI and CITAL may serve as quantitative markers of 5‐HT innervation density, at least in vitro, whereas 6‐NTQ demonstrates a certain lack of specificity and sensitivity. Further work will be needed to assess the potential of CYI and CITAL for positron emission tomographic studies of living brain. Such empirical testing should also be applicable for screening radioligands of the dopamine or the noradrenali
ISSN:0887-4476
DOI:10.1002/syn.890210206
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1995
数据来源: WILEY
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6. |
Elevations of nucleus accumbens dopamine and DOPAC levels during intravenous heroin self‐administration |
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Synapse,
Volume 21,
Issue 2,
1995,
Page 140-148
Roy A. Wise,
Paola Leone,
Robert Rivest,
Kira Leeb,
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摘要:
AbstractExtracellular dopamine and DOPAC (3,4‐dihydroxyphenylacetic acid) levels in nucleus accumbens were sampled by microdialysis and quantified with high‐ performance liquid chromatography during intravenous heroin self‐administration sessions in rats. Dopamine levels in 10 and 20 min samples were elevated following the first injection of each session, reaching a plateau of elevation within the first two or three injections and falling back toward baseline only when drug access was terminated. Elevations were in the range of 150–300% when unit dosages of 0.05–0.2 mgkg were given. Increasing the work requirement from FR‐1 to FR‐10 did not appear to alter the degree of elevation of dopamine levels, and dopamine levels fell during extinction while lever‐pressing rates increased 20‐fold. While animals compensated for unit dose changes between 0.05 and 0.2 mg/kg/injection, adjusting their response rate such that the same hourly drug intake and the same asymptotic dopamine levels were maintained across these conditions, at 0.4 mg/kg/injection hourly drug intake and asymptotic dopamine levels were elevated beyond the levels sustained by the lower doses. These findings confirm that self‐administered doses of intravenous heroin are sufficient to activate the mesolimbic dopamine system and suggest that significant heroin “craving” can emerge when dopamine levels are still moderately elevated, long before the development of dopamine depletion associated with opiate withdrawal.
ISSN:0887-4476
DOI:10.1002/syn.890210207
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1995
数据来源: WILEY
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7. |
Power spectral analysis of electroencephalographic desynchronization induced by cocaine in rats: Correlation with evaluation of noradrenergic neurotransmission at the medial prefrontal cortex |
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Synapse,
Volume 21,
Issue 2,
1995,
Page 149-157
Alice Y. W. Chang,
Terry B. J. Kuo,
T. H. Tsai,
C. F. Chen,
Samuel H. H. Chan,
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摘要:
AbstractWe applied continuous, on‐line and real‐time spectral analysis of electro‐ encephalographic (EEG) signals and microdialysis to evaluate the possible participation of noradrenergic neurotransmission at the medial prefrontal cortex (mPFC) in EEG desynchronization induced by cocaine. Male Sprague‐Dawley rats that were under chloral hydrate anesthesia were used. Intravenous administration of cocaine (1.5 or 3.0 mg/kg) dose‐dependently induced EEG desynchronization, as represented by a decrease in root mean square (RMS) and an increase in mean power frequency (MPF) value of the EEG signals. Power spectral analysis further revealed that whereas both doses of cocaine promoted a reduction in the α (8–13 Hz), θ (4–8 Hz), and δ (1–4 Hz) components, the lower dose of cocaine decreased, and the higher dose increased the β band (13–32 Hz). Microdialysis data indicated an elevation in extracellular concentration of norepinephrine at the mPFC that paralleled temporally and correlated positively with the maximal effect of cocaine on EEG activity. Bilateral microinjection of the selective noradrenergic neurotoxin, DSP4 (50 μg), or equimolar concentration (500 pmol) of the α1‐aladrenoceptor antagonist, prazosin, or α2‐adrenoceptor antagonist, yohimbine, into the mPFC significantly blunted the decrease in δ component (prazosin) or both β and θ components (DSP4 or yohimbine) of EEG activity by the lower dose of cocaine. On the other hand, the same pretreatments appreciably antagonized the increase in β band by cocaine at 3.0 mg/kg. The potency of the antagonism by yohimbine, however, was higher than prazosin. These results suggest that cocaine may elicit EEG desynchronization via noradrenergic neuro‐ transmission, and that α2‐adrenoceptors, and to a lesser extent, α1‐adrenoceptors, at the mPFC may be involved in the subtle dose‐dependent changes in individual EEG s
ISSN:0887-4476
DOI:10.1002/syn.890210208
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1995
数据来源: WILEY
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8. |
CCKBreceptors mediate CCK‐8S‐induced activation of dorsal hippocampus CA3pyramidal neurons: An in vivo electrophysiological study in the rat |
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Synapse,
Volume 21,
Issue 2,
1995,
Page 158-168
Benjamin Gronier,
Guy Debonnel,
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摘要:
AbstractThe sulphated octapeptide C‐terminal fragment of cholecystokinin (CCK‐8s) is present in high concentration in the mammalian brain, where it acts via two types of receptor denoted CCKA, and CCKB. In the dorsal hippocampus, CCK‐8S exerts a potent excitatory effect on pyramidal neurons. The present electrophysiological study was undertaken to determine which CCK receptor type mediates this neuronal activation. Using in vivo extracellular unitary recordings of CA3pyramidal hippocampal neurons, we compared the effect of SNF‐8702, a potent selective CCKB receptor agonist, to that of CCK‐BS, and assessed the effects of selective CCKA, and CCKB, antagonists. CCK‐8S and SNF‐8702, microiontophoretically applied on the same neurons produced a similar degree and pattern of activation. Both CCK‐8s‐ and SNF‐8702‐induced activations were suppressed by the microiontophoretic application of the CCKBantagonist CI‐988, but not by that of the CCKA, antagonist SR 27897. CCK‐8s‐induced activation was not significantly modified by the intravenous administration of the CCK, antagonists devazepide and SR 27897. However, it was reduced by the CCKBantagonist PD 135158, administered intravenously or intracerebroventricularly, and by the intravenous administration of the CCK, antagonist L‐365,260. The intravenous administration of PD 135158 also reduced SNF‐8702‐induced activations. These results indicate that CCKB, receptors mediate CC K‐8S‐induced activation of rat CA3pyra
ISSN:0887-4476
DOI:10.1002/syn.890210209
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1995
数据来源: WILEY
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9. |
Superoxide radicals mediate the biochemical effects of methylenedioxymethamphetamine (MDMA): Evidence from using CuZn‐superoxide dismutase transgenic mice |
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Synapse,
Volume 21,
Issue 2,
1995,
Page 169-176
Jean Lud Cadet,
Bruce Ladenheim,
Hiroshi Hirata,
Richard B. Rothman,
Syed Ali,
Elaine Carlson,
Charles Epstein,
Timothy H. Moran,
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摘要:
AbstractThe subacute and long‐term biochemical effects of methylenedioxymeth‐amphetamine (MDMA) were assessed in homozygous and heterozygous transgenic (Tg) mice that carry the complete sequence of the human copper‐zinc (CuZn) superoxide dismutase (SOD) gene. Non‐transgenic (Non‐Tg) mice showed significant decreased in striatal dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) levels both at 24 h and at 2 weeks after a single injection of MDMA (50 mg/kg). Heterozygous SOD‐Tg mice showed DA depletion only at the 24 h time point. In contrast, homozygous SOD‐Tg mice show no DA or DOPAC depletion at either the 24 h or at the 2 week time points. Moreover, three injections of MDMA (50 mg/kg) given 24 h apart also caused marked reduction of striatal DA and DOPAC in Non‐Tg mice when these substances were measured 2 weeks after the last MDMA injection. That injection schedule also caused small decreases in DA levels in the heterozygous animals but no changes in the homozygous mice; DOPAC levels were not affected in the heterozygous nor in the homozygous SOD‐Tg mice. Furthermore, the multiple injection schedule caused significant decreases in DA and DOPAC in female Non‐Tg mice but not in the two strains of transgenic mice. Neither the single dose nor the multiple dose schedule of MDMA injections affected striatal serotonin (5‐HT) and 5‐hydroxyindoleacetic acid (5‐HIM)levels in any of the three strains of mice. These results support previous observations that MDMA‐induced biochemical effects are observed in the DA systems of mice, whereas these effects are seen in the 5‐HT systems of rats. The present observations also document for the first time a role for the production of superoxide radicals in these effects of MDMA. These mice are an important tool for dissecting pathways involved in drug‐induced neurotoxicity. © 1995 Wiley‐Liss, Inc.1This article is a US Government work and, as such, is in the public doma
ISSN:0887-4476
DOI:10.1002/syn.890210210
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1995
数据来源: WILEY
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10. |
Spare receptors and intrinsic activity: Studies with D1dopamine receptor agonists |
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Synapse,
Volume 21,
Issue 2,
1995,
Page 177-187
Val J. Watts,
Cindy P. Lawler,
Andrea J. Gonzales,
Qun‐Yong Zhou,
Olmer Civelli,
David E. Nichols,
Richard B. Mailman,
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摘要:
AbstractThe intrinsic activities of selected dopamine D1receptor agonists were compared in three distinct molecular expression systems, C‐6, Ltk, and GH4, cells transfected with primate D1Areceptors. The influence of the cell expression system on intrinsic activity varied markedly among agonists. Dihydrexidine (DHX), a potent full agonist with dramatic antiparkinsonian actions, displayed intrinsic activity similar to dopamine in all three cell lines. In contrast, SKF82958 and SKF38393 (full and partial agonists, respectively, in rat striatum) had intrinsic activities equal to dopamine in GH4, cells that expressed a high density of D1receptors, yet were of lower intrinsic activity in C‐6 cells having 15‐fold fewer receptors. The idea that spare receptors are one important determinant of observed intrinsic activity was explored directly by “receptor titration”, in which ca. 90% of D1receptors in Ltk cells were inactivated using EEDQ, an irreversible antagonist. Whereas EEDQ pretreatment decreased the potency of all agonists, it changed the intrinsic activity of some, but not all, drugs. A 40% decrease was seen with the partial agonist SKF38393, and, surprisingly, a 30% decrease was seen with the purported full agonist SKF82958. Conversely, the intrinsic activity of DHX and A68930 were unaffected by the EEDQ treatment. The data demonstrate that significant and biologically meaningful differences in intrinsic efficacy (e.g., DHX vs. SKF82958) may be obscured in test systems that have sufficient receptor reserve (e.g., the striatum). Such differences in intrinsic efficacy may be an important predictor of the clinical utility of D1agonists. © 1995 Wiley
ISSN:0887-4476
DOI:10.1002/syn.890210211
出版商:Wiley Subscription Services, Inc., A Wiley Company
年代:1995
数据来源: WILEY
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