摘要:

AbstractThe ultrastructure and cellular associations of septal efferent terminals identified by anterograde degeneration with neurons containing neuropeptide Y (NPY) in the rat dentate gyrus were examined quantitatively. For this, the septal complex (i. e., medial septal and diagonal band nuclei) of adult male rats was injected with the neurotoxin ibotenic acid (1%; 150 nl) and following a 2–4‐day survival period, the hippocampal formation was processed for the electron microscopic immunocytochemical demonstration of NPY using the avidin‐biotin complex method.Terminals with the morphological characteristics of anterograde degeneration, in particular an increase in osmiophilia, and neurons containing NPY‐like immunoreactivity (NPY‐LI) were most abundant in the hilus of the dentate gyrus. In this region, degenerating terminals (n = 109) were usually small (0.2–0.4 μm in diameter) and formed both asymmetric and symmetric synapses with small (distal) dendrites. The degenerating terminals contacted either single NPY‐containing (19%) perikarya or dendrites or unlabeled (48%) perikarya or dendrites. Some degenerating terminals contacted the same perikarya or dendrites as an NPY‐containing terminal (11%); these neurons were either immunoreactive for NPY or unlabeled. The remaining degenerating terminals were either directly apposed without glial intervention to unlabeled and NPY‐labeled terminals (11%) or lacked associations with any neuronal processes in the plane of section analyzed (11%). The findings demonstrate that ibotenic acid injections in the septal complex can identify septal efferent terminals by degeneration and provide cellular substrates for the direct synaptic regulation as well as presynaptic modulation of hippocampal NPY‐containing neurons by septal efferent terminals. ©

ISSN:0887-4476    

DOI:10.1002/syn.890140202

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

年代:1993

数据来源: WILEY

摘要:

AbstractRecent advances in the cloning of dopamine receptor subtypes have resulted in the detection of at least 5 genetically distinct subtypes of the dopamine receptor. The dopaminergic agonist, quinpirole, has relatively high affinity for the cloned D‐2, D‐3, and D‐4 receptor subtypes. The D‐3 receptor is unique within these 3 subtypes in that it does not appear to have sensitivity to guanine nucleotides. In order to localize the brain regions containing these subtypes of the dopamine receptor, the distribution of [3H]quinpirole binding sites in the rat brain was mapped by autoradiography. Labelling in the absence and presence of the nonhydrolyzable GTP analog, guanylyl‐5′‐imidodiphosphate (Gpp(NH)p) allowed differentiation between the high affinity agonist conformation of the D‐2 receptor and the D‐3 receptor. The highest densities of [3H]quinpirole binding were found in the caudate‐putamen, nucleus accumbens, islands of Calleja, and olfactory tubercle which is consistent with the distribution of dopamine receptors seen with “classical D‐2” receptor agonist and antagonist radioligands. In the presence of 10 μM Gpp(NH)p, binding was reduced in all these areas with the exception of the islands of Calleja. Additional areas which exhibited no change in binding when incubated with Gpp(NH)p included the nodulus and floculus of the cerebellum. Several areas exhibited a partial reduction in binding including the glomerular layer of the olfactory bulb, nucleus accumbens, and the superior colliculus. The distribution of these subtypes is consistent with the distribution of mRNA for the D‐2 and D‐3 receptor in the brain. Therefore, [3H]quinpirole binds to the high affinity agonist conformation of the D‐2 and the D‐

ISSN:0887-4476    

DOI:10.1002/syn.890140203

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe electrophysiological actions of cocaine hydrochloride (COC) on medial prefrontal cortical (mpfc) and hippocampal dentate granule (DG) neurons were investigated in rat brain slices with intracellular recording techniques. The following parameters were measured: resting membrane potential (RMP), spike threshold, spike firing adaptation, postspike train afterhyperpolarization (AHP), excitatory postsynaptic potentials (EPSPs), and inhibitory postsynaptic potentials (IPSPs). In the mpfc, COC appeared to have both inhibitory and excitatory effects. In the majority of cells examined, the EPSP amplitude was attenuated by COC (200 nM–20 μM), whereas the amplitude of the postspike train afterhyperpolarization (AHP) was reduced (an excitatory effect). In DG neurons, 1 μM COC caused a small depolarization. COC potentiated the EPSPs at 1 μM but attenuated EPSPs and IPSPs at 10–100 μM. The amplitude of antidromically evoked EPSPs was also increased by 20 μM COC. At concentrations of 10 μM and greater, COC increased spike threshold. It is concluded that COC actions on mpfc and DG neurons are both excitatory and inhibitory and that these effects may be mediated by multiple neurotransmitters/modulators. © 1993 Wiley

ISSN:0887-4476    

DOI:10.1002/syn.890140204

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe first successful in vivo imaging of monoamine vesicular transporters in the living primate brain is described, using [11C]tetrabenazine ([11C]TBZ) and Positron Emission Tomography (PET). Radioligand uptake into brain is rapid, and at short time periods (10‐30 minutes) the higher uptake and retention of the radiotracer in the more densely dopaminergic innervated striatum is clearly visualized. Specific binding in striatum can be entirely blocked with co‐administration of a pharmacological dose (1 mg/kg i. v.) of tetrabenazine. In a unilaterally MPTP‐lesioned monkey, specific binding of radioligand was absent in the striatum on the lesioned side, with no effect on radiotracer distribution in the cortex, cerebellum or contralateral striatum. PET imaging with [11C]TBZ provides a new approach to the in vivo study of monoaminergic neurons and their loss in neurodegenerative diseases. © 1993 Wiley‐L

ISSN:0887-4476    

DOI:10.1002/syn.890140205

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

年代:1993

数据来源: WILEY

摘要:

AbstractNucleus basalis (NB) neurons are a primary source of neocortical acetylcholine (ACh) and likely contribute to mechanisms of neocortical activation. However, the functions of neocortical activation and its cholinergic component remain unclear. To identify functional consequences of NB activity, we have studied the effects of NB stimulation on thalamocortical transmission. Here we report that tetanic NB stimulation facilitated field potentials, single neuron discharges, and monosynaptic excitatory postsynaptic potentials (EPSPs) elicited in middle to deep cortical layers of the rat auditory cortex following stimulation of the auditory thalamus (medial geniculate, MG). NB stimulation produced a twofold increase in the slope and amplitude of the evoked short‐latency (onset 3.0 ± 0.13 ms, peak 6.3 ± 0.21 ms), negative‐polarity cortical field potential and increased the probability and synchrony of MG‐evoked unit discharges, without altering the preceding fiber volley. Intracortical application of atropine blocked the NB‐mediated facilitation of field potentials, indicating action of ACh at cortical muscarinic receptors. Intracellular recordings revealed that the short‐latency cortical field potential coincided with a short‐latency EPSP (onset 3.3 ± 0.20 ms, peak 5.6 ± 0.47 ms). NB stimulation decreased the onset and peak latencies of the EPSP by about 20% and increased its amplitude by 26%. NB stimulation also produced slow membrane depolarization and sometimes reduced a long‐lasting IPSP that followed the EPSP. The combined effects of NB stimulation served to increase cortical excitability and facilitate the ability of the EPSP to elicit action potentials. Taken together, these data indicate that NB cholinergic neurons can modify neocortical functions by facilitating thalamocortical synaptic transmission. © 19

ISSN:0887-4476    

DOI:10.1002/syn.890140206

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

年代:1993

数据来源: WILEY

摘要:

AbstractIn the present study, we investigated the neural mechanisms of corticotropin‐releasing factor (CRF) and the interactions among CRF, norepinephrine (NE), and N‐methyl‐D‐aspartate (NMDA) systems in the dentate gyrus (DG) of hippocampus in modulating the memory process of rats. One‐way passive avoidance task was adopted. Results indicated that CRF (80 ng), when directly injected into the DG, consistently and significantly enhanced memory retention in rats. The noradrenergic neurotoxin DSP‐4, at a high dose (4 μg), impaired memory. DSP‐4 at a moderate dose (2 μg), which did not affect retention alone, antagonized the memory‐enhancing effect of CRF. Similarly, the ß‐adrenergic antagonist propranolol, at a high dose (8 μg), reduced retention. At a low dose (80 ng), which did not markedly affect retention by itself, propranolol also prevented the memory‐improving effect of CRF. Moreover, direct NE infusions to the DG significantly improved retention performance in a dose‐sensitive manner. Coadministration of CRF and NE did not further enhance retention. These results together suggest that CRF and NE facilitated memory probably through the same instead of independent mechanisms. In contrast, the selective NMDA receptor antagonists 2‐amino‐5‐phosphonopentanoate (AP5) and MK801, at high doses markedly impaired memory retention (0. 8 and 3. 2 μg for AP5, 2 and 10 μg for MK801). At a dose of MK801 that did not significantly alter retention alone (80 ng), it completely blocked the memory‐facilitating effect of CRF. These results indicate that CRF enhanced memory indirectly through NMDA receptor mediation also. Finally, MK801 at 80 ng also successfully antagonized the memory‐facilitating effect of NE in the DG. We have demonstrated that MK801, at the dose chosen for interaction studies, did not markedly alter locomotor activity. These results together suggest that CRF, through a presynaptic facilitation mechanism, possibly facilitates NE release in the DG: increased NE release and stimulation of ß‐adrenergic receptors in the DG result in NMDA receptor activations in the same area. This sequence of events enhance the memory consolidation process in the hippocampus and explained the neural mechanism of CRF in facilitating retention performance in rats. The same neuropeptide/neurotransmitter interactions may have other physiological and neuropathologi

ISSN:0887-4476    

DOI:10.1002/syn.890140207

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

年代:1993

数据来源: WILEY

摘要:

AbstractFentanyl and its derivatives are considered among the most potent opiate analgesic/euphoriants. The pharmacological literature generally supports a μ opiate receptor site of action for the fentanyl derivatives, but some observations suggest that other sites of action may be involved in producing the extremely potent fentanyl effects. In order to investigate the mechanism of action of fentanyl‐like drugs further, [3H]carfentanil was used as a radioligand to image high‐affinity carfentanil binding sites in slidemounted sections of the rat brain (receptor autoradiography). In parallel studies the prototypical μ opiate agonist radioligand [3H]DAMGO ([D‐Ala2‐MePhe4‐Glyol5]enkephalin) was also used. The working hypothesis was that if carfentanil was acting through another high‐affinity site besides the μ opiate receptor, the distribution pattern of the autoradiographic image produced by [3H]carfentanil should be significantly different than the autoradiographic image produced by [3H]carfentanil should be significantly different than the autoradiographic pattern displayed by the well‐characterized and selective μ opiate [3H]DAMGO. Thirty‐five brain regions were examined for specific [3H]carfentanil and [3H]DAMGO binding. The absolute and relative densities of the sites were essentially identical. The highest levels of binding were observed in the “patch” areas of the striatum (131 ± 5 fmol/mg T. E. for [3H]carfentanil; 162 ± 13 fmol/mg T. E. for [3H]DAMGO). The lowest levels were observed in the cerebellum where no specific binding of either radioligand was observed. The overall distribution pattern of the two radioligands produced a correlation coefficient of 0.95; the distribution pattern was prototypical for the μ opiate receptor as reported previously by other groups. Despite the nearly identical distribution patterns, an intriguing difference in the interaction of DAMGO and carfentanil with the μ opiate receptor was observed. The biologically active nonhydrolyzable analog of GTP, GTPγS, was able to completely abolish or greatly diminish specific [3H]DAMGO binding depending on brain region; GTPγS had little or no effect on specific [3H]carfentanil binding. This latter difference in the molecular interaction of DAMGO and carfentanil with the μ opiate receptor may indicate that some of the observed differences in the effects of fentanyl‐like opiates may be due to a difference in the intrinsic activity of the fentanyl derivatives at the μ opiate

ISSN:0887-4476    

DOI:10.1002/syn.890140208

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

年代:1993

数据来源: WILEY

摘要:

AbstractPrevious research has revealed a role of repeated D1dopamine receptor stimulation in the development of behavioral sensitization to the D1/D2agonist apomorphine. The present experiments assessed the role of repeated D1receptor stimulation in neurochemical changes accompanying locomotor sensitization to apomorphine. To assess direct effects of D1stimulation on dopamine synthesis, rats were injected with the D1agonist SKF 38393 (8 mg/kg), followed by an injection with the 3,4‐dihydroxyphenylalanine (DOPA) decarboxylase inhibitor, NSD‐1015. DOPA accumulation, assessed in striatal, nucleus accumbens‐olfactory tubercle (NAOT), and ventral mesencephalon (VM) tissue samples, was not affected by acute SKF 38393. In the second experiment, rats were treated with 10 daily injections of vehicle, apomorphine (5 mg/kg) or the D1agonist SKF 38393 (8 or 16 mg/kg). Daily measures of locomotor activity demonstrated a progressive increase in the apomorphine‐treated rats, but not the SKF 38393‐treated rats, across the 10 days. On day 11, all rats were injected with NSD‐1015 for measurement of DOPA accumulation. Dopamine synthesis was enhanced in the striatum after repeated apomorphine treatment. In contrast, repeated SKF 38393 treatment resulted in either a small decrease or no change in DOPA accumulation in the different brain regions (striatum, NAOT, VM). In the third experiment, tissue levels of dopamine, 3,4‐dihydroxyphenylacetic acid (DOPAC) and [3H]SCH 23390 binding to D1receptors were measured in rats treated with 10 daily injections of vehicle, apomorphine (5 mg/kg), or SKF 38393 (16 mg/kg). In the striatum and NAOT, none of the repeated drug treatments had an effect on DOPAC or dopamine levels. In the VM, DOPAC levels were enhanced following repeated apomorphine, but not repeated SKF 38393, whereas dopamine levels were not affected by either drug treatment. D1binding was not altered by the repeated drug treatments. Since repeated D1stimulation by SKF 38393 did not produce the same alterations in dopamine synthesis and DOPAC levels as repeated apomorphine, the neurochemical effects accompanying locomotor sensitization to apomorphine probably are not mediated by D1receptors. © 1993 W

ISSN:0887-4476    

DOI:10.1002/syn.890140209

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

年代:1993

数据来源: WILEY

摘要:

AbstractDecreased dopaminergic function has been postulated to underlie cocaine addiction. To examine the possibility that dysfunction of brain regions subserved by the dopamine system could promote cocaine self‐administration, positron emission tomography and a dual‐tracer approach was used to examine dopamine D2receptor availability and regional brain glucose metabolism in cocaine abusers. When compared to normal controls, cocaine abusers showed significant decreases in dopamine D2receptor availability which persisted 3‐4 months after detoxification. Decreases in dopamine D2receptor availability were associated with decreased metabolism in several regions of the frontal of these brain areas which are involved in the channeling of drive and affect could lead to loss of control resulting in compulsive drug‐taking behavior. © 1993 Wiley

ISSN:0887-4476    

DOI:10.1002/syn.890140210

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

年代:1993

数据来源: WILEY

摘要:

AbstractPrevious studies have shown that tryptamine (T) is closely associated with the serotonergic system but have failed to determine whether neurons containing only T exist in the raphe nuclei (RN) and/or if T colocalizes with serotonin (5‐HT). The use of rabbit‐conjugated T antisera (TAS) and rat‐conjugated 5‐HT antisera (5‐HTAS) in a double‐labelling technique has made the study of the colocalization of T and 5‐HT in neurons of the rat dorsal RN (DR) possible. Slices taken from the same zone of the DR were treated following four different procedures of double‐immunolabelling: DAB coloration for the rabbit TAS and DAB‐nickel coloration for the rat 5‐HTAS either first or second; or DAB coloration for the 5‐HTAS and DAB‐nickel coloration for the TAS first or second. Control sections were treated according to a single immunoperoxidase staining in the same zone. The immunolabelled neurons were computed using the Biocom 200 program at the same magnification. The results of this double‐immunolabelling show that three different cell types exist in the rat DR: (1) T‐only‐containing neurons, (2) 5‐HT‐only‐containing neurons displaying either homogeneous DAB or homogeneous DAB‐nickel, and (3) neurons where T colocalizes with 5‐HT (T‐positive/5‐HT‐positive neurons) displaying heterogeneous DAB‐nickel coloration. The results were identical whatever the procedure performed or the order of the DAB‐nickel revelation. In contrast, the single immunolabelling method failed to stain T‐only‐containing neurons (or 5‐HT‐only‐containing neurons); T‐immunoreactive cells (or 5‐HT‐immunoreactive cells) correspond in fact to neurons co

ISSN:0887-4476    

DOI:10.1002/syn.890140211

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

年代:1993

数据来源: WILEY