摘要:

AbstractThe diphenylpyrazolidinone cholecystokinin‐B (CCK‐B) antagonist LY262691 has been shown to decrease the number of spontaneously active dopamine (DA) cells in the ventral tegmental area (Al0) and substantia nigra (A9) of the anesthetized rat. In the present study, we examined the localization of the receptors mediating these effects of LY262691 on A9 and A10 DA cells. In one group of anesthetized rats, the effects of systemic administration of LY 262691 on the number of spontaneously active A9 or A10 DA cells was determined using extracellular, single‐unit recordings after radio frequency lesions were placed in the nucleus accumbens, caudate‐putamen, or medial prefrontal cortex. Lesions of the caudate‐putamen blocked the effects of systemically administered LY262691 on the number of spontaneously active A9, but not A10, DA cells. Conversely, lesions of the n. accumbens blocked the effects of systemically administered LY262691 on A10, but not. A9, DA cells. Lesions of the medial prefrontal cortex blocked the effects of systemically administered LY262691 on both A9 and A10 DA cells. In a separate group of anesthetized rats, the number of spontaneously active A9 or A10 DA cells was determined after LY262691 was microinjected into the n. accumbens, caudate‐putamen, or medial prefrontal cortex. Microinjection of LY262691 into the caudate‐putamen led to a significant decrease in the number of spontaneously active A9, but not A10, DA cells. Conversely, microinjection of LY262691 into the n. accumbens or medial prefrontal cortex led to a significant decrease in the number of spontaneously active A10, but not A9, DA cells. Microinjection of a structurally related CCK‐A antagonist (LY219057) into the n. accumbens or medial prefrontal cortex did not affect the number of spontaneously active A10 DA cells, and microinjection of LY219057 into the caudate‐putamen did not affect the number of spontaneously active A9 DA cells. These results indicate that, consistent with known feedback pathways between forebrain structures and midbrain DA neurons, the effects of LY262691 on A9 cells are mediated, at least in part, by antagonism of CCK‐B receptors in the caudate‐putamen, whereas the effects of LY262691 on A10 cells are mediated, at least in part, by antagonism of CCK‐B receptors in the n. accumbens and medial prefrontal cortex.

ISSN:0887-4476    

DOI:10.1002/syn.890150202

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe efferent connections of the sub‐pallidal regions to the mediodorsal thalamic nucleus, the subthalamic nucleus, the lateral hypothalamic area, and the midbrain were investigated in the cat, usingPhaseolus vulgaris—leucoagglutinin (PHA‐L) as an anterograde label. The results indicate that the sub‐pallidal regions of the cat project to the (dorso)medial tip of the subthalamic nucleus and the adjoining lateral hypotha‐lamic area as well as to the ventral tegmental area and the greater extent of the dorsolateral tier of the substantia nigra pars compacta. Extensive projections were also found to the peripeduncular nucleus. The central gray as well as the mesencephalic locomotor region receive some input from the basal forebrain too. In contrast only very limited projections were found to the mediodorsal thalamic nucleus. The results are discussed in view of the possible role of these output regions in oro‐facial dyskinesia. © 1993 Wil

ISSN:0887-4476    

DOI:10.1002/syn.890150203

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

年代:1993

数据来源: WILEY

摘要:

AbstractParoxetine, an antidepressant with a high affinity for serotonin (5‐HT) re‐uptake sites, is a potential tracer of these sites. We determined the kinetic properties of [3H]paroxetine in rat brain in vivo. Relative to [14C]iodo‐antipyrine, the brain uptake index (BUI) of [3H]paroxetine was 60–70%. The unidirectional blood clearance of [3H]paroxetine were 0.05–0.12 ml g−1min−1, lower than expected from the BUI values. The steady state volume of distribution was 3.5 ml hg−1in the diencephalon and 1.8 ml−1in the cerebellum, suggesting a binding potential of unity. Autoradiographs at four hours after [3H] paroxetine injection (300 μCi, i.p.) revealed heterogenous binding consistent with the calculated binding potentials. Binding was nearly absent from cerebellum and was highest in the dorsal raphé, superior colliculus, dorsal hypothalamus, and entorhinal cortex, but did not reach equilibrium in four hours of tracer circulation. The specific binding relative to vermis was displaced by pretreatment with fluonotino (10 mg/kg, i.p.). ©

ISSN:0887-4476    

DOI:10.1002/syn.890150204

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

年代:1993

数据来源: WILEY

摘要:

Abstract[11C]WIN 35,428 was evaluated as a specific in vivo radioligand for the dopamine transporter site by PET scanning in nonhuman primates and humans. In studies with a baboon (Papio anubis), [11C]WIN 35,428 accumulated in brain regions containing dopamine transporters, i.e., the striata. This accumulation was Partially blocked by prior administration of (−)cocaine (4 mg/kg, i.v. ). Placement of a unilateral lesion of dopamine‐containing nerve terminals with MPTP resulted in a unilateral reduction in [11C]WIN 35,428 accumulation in the striatum on the side of the lesion. Imaging of D2dopamine receptors with [11C]NMSP in the same MPTP‐treated animals showed much less reduction in the postsynaptic D2dopamine receptors as compared to the much larger reduction in the dopamine transporters labeled with [11C]WIN 35,428.A total of ten normal human volunteers (five males and five females) with ages ranging from 19 to 81 years were studied. The caudate/cerebellar and putamen/cerebellar ratios ranged from 4.4 to 5.7 90 min after injection of the tracer. Preliminary kinetic modeling with arterial plasma sampling resulted in an average binding potential (K3/K4) of 4.98 in the caudate nucleus and 5.13 in putamen. To demonstrate in vivo blockade with dopamine reuptake inhibitors, two subjects received prior oral doses of 6 mg mazindol. Subject 5 had significant reductions of 29% in the caudate/cerebellar ratio at 90 min, 35% in the putamen/cerebellar ratio at 90 min, 45% in the caudate k3/k4ratio from 6.7 to 3.7, and 46% in the putamen k3/k4from 4.7 to 2.5. Subject 8 had significant reductions of 20% in both the caudate/cerebellar ratio and the putamen/cerebellar ratio at 90 min.During the human PET studies, a number of neuropsychological tests and physiological measurements were performed. No significant changes were found after administration of the [11C]WIN 35,428 alone. Taken together, these data indicate that [11C]WIN 35,428 is a promising radioligand for future studies of neuropsychiatric disorders that involve the dopamine transporter site. © 1993 Wiley‐Liss, Inc.This article is a US government work and as such, is in the public domain in the United States of

ISSN:0887-4476    

DOI:10.1002/syn.890150205

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe 5‐HT3agonist 2‐methyl‐5‐HT had previously been shown to enhance the electrically evoked release of [3H]5‐HT from preloaded slices of the guinea pig brain. In the present study, 2‐methyl‐5‐HT (1 μM) was also found to increase the K+evoked release of [3H]5‐HT from preloaded slices of the guinea pig hypothalamus and this effect was blocked by the selective 5‐HT3antagonist ondansetron. In the presence of tetrodotoxin, the enhancement of the K+‐evoked release of [3H]5‐HT by 2‐methyl‐5‐HT in hypothalamus slices was blocked, thus suggesting that the 5‐HT3receptors mediating this effect are not located directly on 5‐HT terminals. In agreement with this, 2‐methyl5‐HT did not alter the K+‐evoked release of [3H]5‐HT in a synaptosomal preparation of the same brain structure, even at a concentration 10‐fold greater than that used in the slices. Taken together, these data indicate that these facilitatory 5‐HT3receptors are not located on 5‐HT terminals in the guinea pig hypothalamus and therefo

ISSN:0887-4476    

DOI:10.1002/syn.890150206

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

年代:1993

数据来源: WILEY

摘要:

AbstractConditioning stimulation applied to afferent fibers in stratum radiatum or stratum oriens of hippocampal area CA1 produced heterosynaptic, posttetanic depression (PTD) of excitatory postsynaptic potentials (EPSPs). PTD amounted to a 60–80% reduction of EPSPs and recovered over a 5 min period. Conditioning stimulation also induced a posttetanic hyperpolarization (PTH) averaging 4 mV and decaying over a 1–1.5 min period. PTH was accompanied by a large reduction in input resistance. We sought to determine the pre‐ or postsynaptic locus of heterosynaptic PTD. Our results suggest that PTD reflects a presynaptic mechanism: (1) PTD was observed for both N‐methyl‐Daspartate (NMDA) and non‐NMDA receptor mediated EPSPs; (2) Direct depolarization of pyramidal cells, substituted for the synaptic depolarization induced by conditioning stimulation, did not elicit PTD; (3) PTD and PTH were differentially affected by pharmacological and postsynaptic manipulations; (4) Conditioning stimulation depressed responses to pressure applied glutamate, but the magnitude and duration were too small to account for PTD. Since afferent fiber volleys were not depressed following conditioning stimulation, while field EPSPs were, we conclude that conditioning stimulation suppresses synaptic release of glutamate. © 1993 Wil

ISSN:0887-4476    

DOI:10.1002/syn.890150207

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

年代:1993

数据来源: WILEY

摘要:

AbstractCocaine produces biochemical alterations in brain serotonin (5‐HT) neurons. Since 5‐HT is critical to the development of fetal 5‐HT neurons and target tissues, we hypothesized that in utero exposure to cocaine could result in long‐term alterations in postnatal 5‐HT systems. Pregnant Sprague‐Dawley rats were administered either saline or (−)cocaine (15 mg/kg, s.c., b.i.d.) from gestational day 13 to 20. Prenatal cocaine exposure did not alter litter size, gender number, or progeny birth weights. Functional alterations in serotonergic systems were determined in postnatal day (PD) 70 male progeny by measuring changes in 5‐HT mediated plasma hormones following a single 8 mg/kg injection of the 5‐HT releaser p‐chloroamphetamine (PCA). Cocaine exposed male progeny exhibited significant reductions in adrenocorticotropic hormone (ACTH, −43%) and renin (−62%) responses to PCA. However, no alterations were observed in the corticosterone or prolactin response to PCA. In utero exposure to cocaine did not alter basal levels of ACTH, renin, corticosterone, or prolactin. There were no significant differences in the density of either hypothalamic or cortical 5‐HT uptake sites. Likewise, there were no significant differences in the densities of any of the 5‐HT1receptor subtypes or in the density of 5‐HT2receptors in cortex. These data, which provide the first demonstration of deficits in 5‐HT mediated neuroendocrine function in adult progeny following in utero exposure to cocaine, indicate long‐term functional alterations of brain 5

ISSN:0887-4476    

DOI:10.1002/syn.890150208

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

年代:1993

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890150201

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

年代:1993

数据来源: WILEY