摘要:

AbstractA novel dopamine receptor mRNA transcript has been identified and classified as the D3receptor subtype. We have examined the binding of the D2/D3‐selective compound [125I]‐Iodosulpride using unlabeled D3‐selective 7‐OH‐DPAT to determine the distribution of D2 and D3 dopamine receptor subtypes in the rat basal forebrain. Use of [125I]‐labeled ligands has significant advantages over [3H]‐labeled compounds for autoradiographic studies, especially for evaluating small brain areas containing low receptor densities. [125I]‐Iodosulpride identified two sites with high affinity (<1 nM) in the presence of (‐)sulpiride (μM; D2+3) or 7‐OH‐DPAT.(10 nM; D3), with a greater density of D2receptors (twofold) compared to D3receptors in the striatum. The density of D2and D3receptor subtypes displayed a 1:1 ratio in the nucleus accumbens. [125I]‐Iodosulpride with 7‐OH‐DPAT displayed D2sites, predominately in the striatum. Digital subtraction autoradiography showed the highest levels of D3binding in the islands of Calleja as well as in the core and shell regions of the nucleus accumbens. In sum, the advantages in using [125I]‐Iodosulpride to label the dopamine receptor subtypes are high specific activity, affinity, and lack of quenching in autoradiographic analyses. Moreover, masking D3 receptors with 7‐OH‐DPAT permitted indirect determination of D3receptor density and localization using the [125I]‐labeled ligand, without the potential confound of 7‐OH‐DPAT binding to sigma receptors. The colocalization of the D2dopamine receptors with D3receptors suggests that unique interactions may exist between the receptor subtypes in the rat basal

ISSN:0887-4476    

DOI:10.1002/syn.890190102

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

年代:1995

数据来源: WILEY

摘要:

AbstractWe had previously demonstrated extrastriatal uptake of [18F]N‐methyl‐spiroperidol (18F‐NMS) in the human brain. This study evaluates the effect of haloperidol on18F‐NMS binding in extrastriatal brain regions. Six schizophrenic patients on haloperidol underwent two PET scans with18F‐NMS at 12 h and at 6 days after haloperidol withdrawal. There was a significant increase in18F‐NMS uptake in striatal, thalamic, and temporal regions but not in frontal, occipital, or cerebellar regions, following drug withdrawal. Haloperidol's ability to block the uptake of18F‐NMS is an indication of the specificity of the radioligand's binding in these regions and supports the postmortem data demonstrating the presence of dopamine D2receptors in the thalamus and temporal cortex of the human brain. © 1995 W

ISSN:0887-4476    

DOI:10.1002/syn.890190103

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe regional distribution of the mRNA encoding the serotonin 5‐HT1Breceptor was studied in the central nervous system of the rat by in situ hybridization histochemistry and Northern blot analysis. A 180 base pair probe, corresponding to a highly selective portion of the third intracellular loop of the rat 5‐HT1Breceptor, was used. In most regions, a single 5 kb message was found by Northern blot analysis. However, two additional bands (2.5 and 4 kb) were detected in the striatum. The rank order of 5‐HT1BmRNA abundance was striatum ≥ septum = ventral tegmentum _‐ colliculi = hypothalamus = hippocampus>brain stem a cerebellum _‐ dorsal horn of the spinal cord>cerebral cortex a ventral horn of the spinal cord>olfactory tubercle. This distribution was confirmed by in situ hybridization, which further revealed that the 5‐HT1BmRNA was present in dorsal root ganglia, the layer IV of the cerebral cortex, the Purkinje cell layer of the cerebellum, the pyramidal neurons in the CAl area of the hippocampus, and the dorsal and median raphe nuclei. In situ hybridization was also performed in nomifensine (10 mg/kg/ i.p.)‐pretreated rats whose serotoninergic neurons were extensively and selectively lesioned by microinjection of 5,7‐dihydroxytryptamine (8 μg/1 μl) directly into the anteroventral vicinity of anterior raphe nuclei 3 weeks before sacrifice. In lesioned rats, 5‐HT1BmRNA was present in the same areas and at the same levels as in control rats, except in the dorsal and median raphe nuclei, where a marked decrease (–75%) in its local concentration was observed. These data provide the first demonstration of the synthesis of 5‐HT1Breceptor within serotoninergic neurons, as expected of their presynaptic autoreceptor function at the level of serotoninergic termina

ISSN:0887-4476    

DOI:10.1002/syn.890190104

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

年代:1995

数据来源: WILEY

摘要:

AbstractPsychostimulant drugs have been reported to increase the expression of some immediate‐early genes in the cerebellum. In the present study, immunohistochemical techniques were used to assess the pattern of c fos expression in the cerebellum produced by d‐amphetamine or cocaine. Systemic administration of d‐amphetamine (1.5, 6 mg/kg) or cocaine (10, 20 mg/kg) increased locomotor activity, which at low doses was blocked by pretreatment with the dopamine D1 receptor antagonist SCH 23390 (1 mg/ kg). Within the cerebellum, basal levels of c fos expression were abolished by SCH 23390, with the exception of lobule VI. Dose‐dependent increases in Fos‐like immunoreactivity were elicited by d‐amphetamine and cocaine. Pretreatment with SCH 23390 greatly reduced the extent to which either stimulant increased c‐fos expression. Psychostimulant‐induced Fos‐like immunoreactive nuclei were generally restricted to the granule cell layer within each of the midvermal cerebellar lobules (I‐X), although occasional nuclei were found in the Purkinje cell layer. In addition, a homogeneous pattern of Fos‐like immunoreactive nuclei, of sparse density, was also found near the pial surface of the molecular layer following d‐amphetamine but not cocaine. Within the granule cell layer dense clusters of Fos‐like immunoreactive neurons extended from the molecular layer to the Purkinje cell layer and were found at both the pial surface as well as in the deep portions of individual folia. These data add to a growing body of evidence indicating that the induction of regionally specific alterations in c‐fos expression by psychostimulants is mediated via a D1 receptor mechan

ISSN:0887-4476    

DOI:10.1002/syn.890190105

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe Milan hypertensive strain (MHS) of rats, in addition to having hypertension, is also characterized by a genetic deficiency in calpastatin, the endogenous inhibitor of calpain. Since this protease has been implicated in long‐term potentiation (LTP), we have investigated whether induction of this form of plasticity was altered in this strain of rats as compared to control animals (Milan normotensive strain, MNS). Progressive induction of LTP by increasing numbers of high frequency trains resulted in a greater degree of potentiation measured with all inducing protocols in MHS as compared with MNS animals. This difference was not related to the hypertension, since another hypertensive strain (the SHR strain) and a segregated Milan hypertensive strain, expressing only the hypertention but not the calpastatin deficiency (the MHNE strain), exhibited an LTP indistinguishable from control rats. Treatment of MHNE rats for 2 months with isovalerylcarnitine, a compound that increases calpain activity, also resulted in a greater amount of LTP induced by high frequency trains. These effects were not related to an enhancement of the NMDA receptor dependent component of responses to burst stimulation. These results are consistent with the idea that conditions under which calpain activation is facilitated are associated with a greater degree of synaptic potentiation. © 1995 Wiley‐Liss,

ISSN:0887-4476    

DOI:10.1002/syn.890190106

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe administration of the neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) to adult cats severely disrupts the dopaminergic innervation of the striatum. Animals display a parkinson‐like syndrome, consisting of akinesia, bradykinesia, postural instability, and rigidity, which spontaneously recovers by 4–6 weeks after the last administration of MPTP. In this study we used quantitative receptor autoradiography to examine changes in DA uptake sites and DA receptors in the basal ganglia of normal, and symptomatic and recovered MPTP‐treated cats.Consistent with the destruction of the nigrostriatal DA pathway, there was a severe loss of DA uptake sites, labeled with [3H]‐mazindol, in the caudate nucleus (64–82%), nucleus accumbens (44%), putamen (63%), and substantia nigra pars compacta (SNc, 53%) of symptomatic cats. Following behavioral recovery, there were no significant changes in DA uptake site density. Significant increases of [3H]‐SCH 23390 binding to D1 DA receptors were observed in the dorsal caudate (>24%; P30%; P36% (P<0.05) following MPTP treatment.These data show that cats made parkinsonian by MPTP exposure have a significant decrease in the number of DA reuptake sites throughout the striatum and that recovery of sensorimotor function in these animals is not correlated with an increase in the number of striatal reuptake sites. Behavioral recovery, however, does seem to be correlated with a general elevation of Dl receptors throughout the striatal complex. The present data also show that direct correlations between changes in DA receptor regulation after a large DA depleting lesion and behavioral deficits or recovery from those deficits are difficult and that the relationships between DA receptors/transporters and behavior require further

ISSN:0887-4476    

DOI:10.1002/syn.890190107

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe purpose of this study was to compare the effects of amphetamine exposure on subsequent amphetamine‐induced changes in behavior and dopamine (DA) release in the dorsal and ventral striatum, as a function of time following the discontinuation of repeated amphetamine treatment. Rats were pretreated with either saline or an escalating‐dose amphetamine regimen, and then received a 0.5 mg/kg amphetamine “challenge” after either 3, 7, or 28 days of withdrawal. Animals tested after 28 days of withdrawal were hypersensitive (sensitized) to the locomotor‐activating effects of amphetamine, and relative to control animals showed a significant enhancement in amphetamine‐stimulated DA release in both the dorsal and ventral striatum, as revealed by in vivo microdialysis. Animals tested after only 3 or 7 days of withdrawal showed neither behavioral sensitization nor enhanced amphetamine‐stimulated DA release. These results establish that time‐dependent changes in behavioral sensitization to amphetamine are associated with time‐dependent changes in amphetamine‐stimulated DA release, and support the hypothesis that persistent sensitization‐related changes in striatal DA neurotransmission contribute to the expression of behavioral sensitization.

ISSN:0887-4476    

DOI:10.1002/syn.890190108

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

年代:1995

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890190101

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

年代:1995

数据来源: WILEY