摘要:

AbstractHippocampal tissue transplanted into the anterior chamber of the eye offers a unique system in which development can be studied in the absensce of the noradrenergic innervation. This system was used to determine the extent to which noradrenergic innervation regulates the developement of adrenergic receptors. In addition to examining single denervated transplates, transplants grown with innervation from the superior cervical ganglia of the host rat or from locus coeruleus cotransplants were also examined to determine whether the source of norepinephrine and extent of innervation in oculo regulate the developement and density of adrenergic receptors. In vitro autoradiographic analysis of ligand binding to both α1‐ and β‐adrenergic receptors. In vitro autoradiographic analysis of ligand binding to both α1‐and β‐adrenergic receptors with125‐I‐BE2254 and125I‐pindolol, respectively, was used to charcterize aderenergic receptors in the intraocular transplants. Quantitative analysis of the receptors showed and up‐regulation of both α1‐ and β‐adrenergic receptors in tissue grown in the absence of norepinephrine, but in general there was not a high degree of correlation between norepinephrine content and receptor density. Although high‐performance liquid chromatography (HPLC) analysis of catecholamines revealed higher than normal amounts of norepinephrine in hippocampal transplants innervated by the superior cervical ganglia or a locus coeruleus cotransplant, the density of α1‐ and βreceptors was quite comparable with values found in the literature for normal adult hippocampus. These results suggest that the relationship between receptor number and density of innervation may differ significantly from what is observed in response to pharmacological manipultion of norepinep

ISSN:0887-4476    

DOI:10.1002/syn.890060202

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe enkephalin analog [2‐D‐Penicillamine, 5‐D‐Penicillamine]enkephalin was radioiodinated125I‐DPDPE and shown to retain a pharmacological selectivity characteristic the delta opioid receptor in in vitro binding studies. The distributions of125I‐DPDPE binding, using in vitro autoradiographic techniques, were similar to those previously reported for the delta opioid receptor. The nucleus accumbens, striatum, and medial prefrontal cortex contain dense gradients of125I‐DPDPE binding within particular regions of the mesocorticolimbic dopamine system. Unilateral lesions of dopamine perikarya (A9 and A10) within the ventral tegmental area nd substantia nigra produced by mesencephalic injection of 6‐hydroxydopamine resulted in significant (20–30%) increase in125I‐DPDPE binding contralateral to the lesion within the striatum and nucleus accumbens. Lesions of the perikarya (dopaminergic and nondopaminergic) of the ventral tegmental area, induced by aquinolinic and injections, caused increases of less magnitude within these same nuclei. No significant alteratons in125I‐DPDPE binding were observed within the mesencephalon as a result of either treatment. The specificity of the lesions was confiremed by immunocytochemistry for tyrosine for tyrosine hydroxylase. These results suggest that the enkephalins and opioid agonists through delta opioid receptors do not dircetly modulate dopaminergic afferents but do regulate postsnaptic targets of the mesocorticol

ISSN:0887-4476    

DOI:10.1002/syn.890060203

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

年代:1990

数据来源: WILEY

摘要:

AbstractAcetylcholine (ACh), acting via muscarinic receptors, is known to modulate neuronal responsiveness in primary sensory neocrotex. The administration of ACh to cortical neurons facilitates or suppresses responses to sensory stimuli, and these effects can endure well beyond the period of ACh application. In the present study, we sought to determine whether ACh produces a general change in sensory information processing, or it canspecificallyalter the processing of sensory stimuli with which it was “paired.” To answer this question, we restricted acoustic stimulation in the presensce of ACh to a single frequency, and determined single neuron frequency receptive fields in primary auditory cortex before and after this pairing. During its adminidstration, ACh produced mostly facilitatory effects on spontaneous activity and on responses to the single frequency tone. Examination of frequency receptive fields after ACh administration revealed receptive field modifications in 56% of the cells. In half of these cases, the receptive field alterations were highly specific to the frequency of the tone previously paired with ACh. Thus ACh can produce stimulus‐specific modulation of auditory information processing. An additional and unexpected finding was that the type of modulation during ACh administration did not predict the type of receptive field modulation observed after ACh administration; this may be related to the physiological “cortext” of the same stimulus in two different conditions. The implications of these findings for learning‐induced plasticity in the auditory cortex i

ISSN:0887-4476    

DOI:10.1002/syn.890060204

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

年代:1990

数据来源: WILEY

摘要:

AbstractLong‐term administration of the atypical neuroleptic clozapine (CLZ) poses a much lower risk of extrapyramidal side effects (EPS) than does the use of typical neuroleptics such as haloperidol (HAL). To investigate the neural mechanisms of the differing CNS activities of these two drugs, we used quantitative autroadiography to measure changes in dopamine and serotonin receptors in rats after injection with CIZ or HAL for 21 days at clinically relevant dose ratios. Levels of D1, D2, and 5‐HT2receptors were determined in frontal cortex, caudate‐putamen, and nucleus accumbens. Rats that received CLZ chronically showed CNS receptor changes markedly different from those in chronic HAL‐treated animals. Whereas rats treated chronically with HAL showed enhanced striatal D2binding (average increase of 42%), those treated with CLZ did not. In contrast, CLZ, but not chronic HAL, induced enhanced striatal D1binding (average increase of 43%). Finally, CLZ treatment decreased 5‐HT2receptor binding by an average of 37%, while HAL had no significant effect. The effects of chronic HAL or CLZ treatment on receptors were similar in all forebrain areas examined. However, since D1and 5‐HT2receptors are more abundant that D2sites in limbic and neocortical areas, the preferential modulation of D1and 5‐HT2receptors by CLZ suggests a greater impact of this atypical neuroleptic on activity of the limbic system than that achieved by the typical neuroleptic, HAL. These findings suggest that the clinical profile of atypical nuroleptics such as CLZ may be attributed to their effects on a receptor profile differing in pharmacological characteristics and anatomical distribution from that affected by typical

ISSN:0887-4476    

DOI:10.1002/syn.890060205

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

年代:1990

数据来源: WILEY

摘要:

AbstractPeripheral injections of the tracer fluorogold (EG) and immunocytochemistry were used to study the modulation gonadotropin‐releasing hormone (GnRH) cell secretory activity in adult mice. Intraperitoneal adminstration of FG would make it available to all GnRH terminals outside the blood‐brain barrier. The degree of capture of the dye would be linked to exocytotic (e.g., secretory) events at the nerve terminal. Single injections of tracer were made into intact mice of both sexes, and this resulted in the retrograde labeling of two‐thirds of the GnRH cell bodies. Administration of identical doses to 3 week castrate mice revealed a reduction in the percentage of GnRH cells, with detectable FG, to 40% of the total. Castration did not diminish the number of GnRH cells visualized. When castrate animals received two doses of FG, the number of GnRH cells with tracer was increased to slightly greater than intact levels. This suggests that the secretory rate of individual GnRH cells might be reduced under coditions of castration. In addition, when ovariectomized females treated with estrogen and progeserone to induce luteinizing hormone (LH) surge were injected with FG just prior to that surge, over 80% of the GnRH neurons were robustly labeled with FG. These latter data are interpreted as representing GnRH neurons at maximally synchronized activity. This study suggests that peripheral administration of FG can be used in this species to follow alterations in neurosecretory

ISSN:0887-4476    

DOI:10.1002/syn.890060206

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

年代:1990

数据来源: WILEY

摘要:

AbstractMedial amygdala neurons responsive to electrical stimulationof the medial septal area were electrophysiologically identified in ovariectomized, urethane‐anesthetized female rats. Peristimulus time histograms were collected and used to define the orthodromic response. The action of iontophoretically applied luteinzing hormone‐releasing hormone (LHRH) and an LHRH fragment, Ac‐LHRH5–10, on the activity of were identified as orthodromically responsive. Three types of orthodromic responses were observed: excitatory, inhibitory, and complex. Priming the animals with 5 μg estradiol benzoate (EB) 48 hr prior to recording had no effect on the overall number of neurons responding to septal area stimulation, but EB priming did significantly reduce the percentage of orthodromically excited neurons. The firing rate of the majority of amygdala neurons responsive to septal area stimularion was not affected by iontophoretically applied LHRH (59 of 76) or LHRH fragment (41 of 65). In some cases, application of LHRH (10 of 76) or Ac‐LHRH5‐10(12 of 55) produced a change in neuronal firing that was similar in direction to the orthodromically evoked response. When applied during the collection of peristimulus time histograms, both peptides were also able to modulate the orthodromically evoked response (five of 18 cells tested with LHRH and three of 14 cells tesed with Ac‐LHRH5‐10). The results demonstrate a large projection from the septal area to the amygdala, one component of which is altered by estrogen priming. The findings suggest that LHRH released from septal neurons may act as a neurotransmitter and a neuromodulator in the medial amygdala; however, the large number of neurons unaffected by the decapeptide indicates that the role of LHRH at this synapse is subservient to that of anothe

ISSN:0887-4476    

DOI:10.1002/syn.890060207

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

年代:1990

数据来源: WILEY

摘要:

AbstractThyrotropin‐releasing hormone (TRH) receptors are widely distributed throughout the nervous systems. In particular, both the dorsal and the ventral horn (VH) neurons contain a rich distribution of TRH receptors, and TRH application to these sites has profound physiological effects. Currently the mechanism of action of TRH is not known. We examined the effect of TRH on ventral horn neurons using intracellular and patch‐clamp techniques. Our results indicate that TRH application profoundly increases the firing rate of VH cells by decreasing membrane conductance. More importantly, TRH causes a significant increase in frequency and amplitude of postsnaptic potentials. Under voltage‐clamp condition, TRH reduces holding current and causes a significant increase in the rate of occurrence and the amplitude of excitatory postsynaptic currents (EPSCS), an effect that lasts for more than 5 minutes. This effect of TRH is not observed in of the EPSCS when it is applied to a region of the cell that is sparsely innervated. These results provide strong evidence that presynaptic mechanisms have a significant role in the excitatory effect of TRH on the VH neurons. Because there is evidence that trophic factors are released from presynaptic terminals, by increasing synaptic activity, TRH can have a trophic influence on the spinal cord neurons. In addition, because there are a significant number of TRH containing neurons within the spinal cord, it is likely that TRH has a major role in information processing within the spinal

ISSN:0887-4476    

DOI:10.1002/syn.890060208

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe intravenous administration of the benzodiazepine inverse agonist DMCM (6,7‐dimethoxy‐4‐ethyl‐β‐carboline‐3‐carboxylic acid methyl ester) dose‐dependently reduced the efficacy of electrial stimulation of the 5‐HT pathway in depressing the firing activity of rat hippocampus pyramidal neurons. This effect was prevented by the benzodiazepine receptor antagonist flumazenil and reversed by the benzodiazepine receptor agonist diazepam. This indicates that DMCM alters‐5HT transmission in the rat dorsal hippocampus via benzodiazepine receptors and that these receptors have both agonist and i

ISSN:0887-4476    

DOI:10.1002/syn.890060209

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

年代:1990

数据来源: WILEY

摘要:

AbstractIntrastratal injection of the glutamate analogue N‐methyl‐D‐aspartate (NMDA, 25 nmol) in postnatal (PND) 7 rats provides a rapid, sensitive, and reproducible assay in which potential neuroprotective strategies against excitotoxic neuronal injury can be examined in vivo. Brain injury is quantified 5 days postinjection by comparison of the weights of the injected and contralateral cerebral hemispheres. Intraperitoneal injections (15 minutes post‐NMDA) of competitive and noncometitive NMDA receptor antagonists attenuated the severity of NMDA‐induced brain injury. The rank order of neuroprotective potency of these antagonists was CGS‐19755

ISSN:0887-4476    

DOI:10.1002/syn.890060210

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe cocaine analog[3H]2β‐carbomethoxy‐3β‐(4‐fluorophenyl)tropane ([3H]CFT or [3H]WIN 35,428) binds with high affinity and selectivity to cocaine receptors in the monkey caudate‐putamen. [3H]CFT was used to map the regional distribution of cocaine binding sites in slide‐mounted sections of monkey brains using autoradiographic techniques. Hemicoronal brain sections were incubated with [3H]CFT (3 nM) alone or in the presence of excess (−)‐cocaine (30 μM) to mask the binding sites. High densities of [3H]CFT binding sites were detecte in the caudate nucleus, putamen, and nucleus accumbens. In all three regions, binding was markedly reduced by coincubatin with unlabeled (−)‐cocaine, indicating low levels of nonspecific binding. Little or no binding was observed in the cortex, thalamus, globus pallidus, or white matter tracts at the levels studied. In order to characterize biding sites for [3H]CFT in tissue sections, competition experiments were conducted using a fixed concentration of [3H]CFT (3 nM) and a range of concentrations of (−)‐cocaine, (+)‐cocaine, CFT, Lu 19‐005, GBR 12909, bupropion, and citalopram. The IC50values for the drugs in tissue sections corresponded closely with their reproted IC50values in monkey caudate‐putamen membranes (r =0.99, p<0.0001), suggesting that [3H]CFT binding is similar in the two preparations. These findings support the view that cocaine receptors labeled by [3H]CFT are localized predominantly in dopmaine‐rich brain regions implicated in the behav

ISSN:0887-4476    

DOI:10.1002/syn.890060211

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

年代:1990

数据来源: WILEY