摘要:

AbstractThe binding of3H‐CN‐IMI to 5‐HT uptake sites, as measured by quantitative autoradiography, was used as a marker of serotonergic neurons. Within the dorsal raphe nucleus the binding of3H‐CN‐IMI was compared in adjacent coronal sections of rat brain to the binding of3H‐DPAT to 5‐HT1Areceptors, which have a known somatodendritic localization. The heterogeneous pattern of binding of these two radioligands within the dorsal raphe nucleus was similar and corresponded to the distribution of serotonergic cell bodies as visualized by 5‐HT immunohistochemistry. Intracerebroventricular administration of 5,7‐dihydroxytryptamine (5,7‐DHT), which caused a dramatic loss of 5‐HT immunoreactivity and3H‐DPAT binding to 5‐HT1Areceptors, resulted in a marked reduction of3H‐CN‐IMI binding in this nucleus. Treatment of rats with a dose of parachloroamphetamine (PCA) which has been reported to selectively lesion serotonergic processes arising from the dorsal raphe nucleus, while sparing serotonergic cell bodies and projections from the median raphe nucleus, did not alter the binding of3H‐DPAT or3H‐CN‐IMI in the dorsal raphe nucleus; serotonergic cell bodies appeared morphologically unaffected. The lack of effect of PCA treatment on the binding of3H‐DPAT and3H‐CN‐IMI is consistent with a somatodendritic localization of the 5‐HT transporter in the dorsal raphe nucleus. PCA treatment appeared to produce a moderate loss of serotonergic innervation in serotonergic terminal field areas as visualized by serotonin immunohistochemistry. The reductions in3H‐CN‐IMI binding observed in terminal field areas (24 to 69%) following treatment of rats with PCA did not reflect a marked differential innervation of forebrain areas by the dorsal and medial raphe nuclei as expected from previous biochemical studies, and were not entirely consistent with the findings of neuroanatomical studies using histochemical techniques. Site‐specific injection of 5,7‐DHT into the dorsal raphe nucleus produced an 80 ± 11% reduction in the binding of3H‐CN‐IMI in this nucleus, whereas the binding of3H‐CN‐IMI in the median raphe nucleus was not reduced. The reductions in3H‐CN‐IMI binding measured in the caudate putamen, frontal and entorhinal cortex as a result of specific lesion of the dorsal raphe nucleus were suggestive of a heavy innervation of these areas by the dorsal raphe nucleus as indicated in neuroanatomical studies. In the hippocampus, our data were consistent with an overlapping innervation of these areas by both the dorsal and median raphe nuclei and are not reflective of predominantt

ISSN:0887-4476    

DOI:10.1002/syn.890170102

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

年代:1994

数据来源: WILEY

摘要:

AbstractIn animals with a large unilateral 6‐hydroxydopamine (6‐OHDA) lesion of the nigrostriatal dopamine (DA) system the traditional “rotational behavior model” states that amphetamine will induce circling behavior towards the denervated striatum (ipsiversive), that is, away from the side where there is greater amphetamine‐stimulated DA release and greater DA receptor stimulation. It is puzzling, therefore, why amphetamine induces contraversive rotation in rats tested 4 days after a unilateral 6‐OHDA lesion, despite a 90‐95% loss of the dopaminergic input to the striatum by this time. Rats reverse their direction of amphetamine‐induced rotation by 8 days post‐lesion and turn in the ipsiversive direction thereafter. To try and resolve this paradox, bilateral striatal microdialysis was used to estimate the effects of amphetamine on DA neurotransmission on Day 4 and Day 8 following a large unilateral 6‐OHDA lesion of the substantia nigra. On Day 4 post‐lesion, amphetamine produced a moderate (around 50% of control) increase in the extracellular concentration of DA in the denervated striatum. This amphetamine‐releasable pool of DA was exhausted by a single amphetamine challenge, because a second injection of amphetamine given 3 h after the first did not produce a comparable increase in DA. It is suggested that on Day 4 post‐lesion the amount of DA released by amphetamine in the denervated striatum is sufficient to produce greater DA receptor stimulation on that side, because of DA receptor supersensitivity, and this leads to contraversive rotation. On Day 8 post‐lesion, amphetamine induced DA release in the intact striatum but had no effect on extracellular DA in the denervated striatum (DA was nondetectable). On Day 8, therefore, DA receptor stimulation would be greatest in the intact striatum, leading to ipsiversive rotation. In conclusion, it is suggested that the seemingly paradoxical reversal in the direction of amphetamine‐induced rotation that occurs over the first week following a unilateral 6‐OHDA lesion is consistent with the traditional rotational model, and is due to time‐dependent changes in the ability of amphetamine to release DA in the denervated

ISSN:0887-4476    

DOI:10.1002/syn.890170103

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

年代:1994

数据来源: WILEY

摘要:

AbstractSeveral reports have suggested that chronic haloperidol (HAL) treatment induces ultrastructural changes in synapses of substantia nigra, corpus striatum, and medial prefrontal cortex (mPFC) of rat brain. The effects of HAL on specific cortical transmitter systems, however, are not well characterized. Recent studies have indicated that there may be a loss of gamma‐aminobutyric acid (GABA)ergic cells in anterior cingulate cortex of schizophrenic subjects and this hypothesis has prompted interest in the question of whether dopamine receptor antagonists, such as HAL, may influence the activity of this transmitter system. This current report describes a quantitative light microscopic analysis of GABA‐immunolabeled axosomatic terminals in mPFC of rats treated with HAL decanoate (0.5 mg/kg/day, i.m.) for a period of 4 months. GABA‐containing terminals were visualized with an avidin‐biotin immunoperoxidase method for localizing anti‐GABA antibodies. Computer‐assisted image processing was employed to determine the total number of pixels representing GABA‐immunoreaction product in axon terminals that were in direct apposition to pyramidal cell bodies. Drug‐treated animals showed a significant increase in the number of pixels representing GABA‐immunoreaction product in axosomatic terminals of layers II, III, V, and VI (93%, 63%, 31%, and 43%, respectively). These data are consistent with the idea that chronic HAL administration may be associated with a significant increase in the amount of GABA present in terminals surrounding pyramidal neurons of rat mPFC. The fact that GABA‐containing terminals showed the greatest increase in layer II is not consistent with the known distribution of dopamine afferents to this region which is lowest in superficial laminae. Based on the laminar distribution of non‐dopaminergic receptor types that have a high affinity for HAL, the effect of this drug on GABAergic transmission could potentially involve changes that are mediated through mechanisms in which 5‐HT2or sigma opiate receptors play a role.

ISSN:0887-4476    

DOI:10.1002/syn.890170104

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

年代:1994

数据来源: WILEY

摘要:

AbstractChanges in calcium (Ca2+) homeostasis have been proposed to contribute to the aging process. Paired‐pulse facilitation, a form of synaptic enhancement that relies upon an accumulation of Ca2+in the presynaptic terminal, was used to examine the effect of aging at the corticostriatal synapse. Intracellular recordings in striatal neurons from young rats demonstrated a consistent enhancement in the second of two synaptic responses evoked by stimulation of the corpus callosum. In contrast, neurons from aged rats showed a consistent depression of the second synaptic response at identical pairing intervals. These differences were not explained by an age‐dependent increase in synaptic depression and demonstrate an alteration in the Ca2+‐mediated process of presynaptic facilitation. © 1994 Wiley‐L

ISSN:0887-4476    

DOI:10.1002/syn.890170105

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

年代:1994

数据来源: WILEY

摘要:

AbstractMany effects resulting from D2dopamine (DA) receptor stimulation are manifest only when D1DA receptors are stimulated by endogenous DA. When D1receptor stimulation is enhanced by administration of selective D1receptor agonists, the functional effects of selective D2agonists are markedly increased. These qualitative and quantitative forms of D1/D2DA receptor synergism are abolished by chronic DA depletion when both D1and D2DA receptors are supersensitive. Using both electrophysiological and behavioral methods, the present study examined the effects of selective D1and D2renaptnr supersensitivity, induced by repeated administration of selective D1or D2receptor antagonists, on the synergistic relationships between D1and D2receptors. Daily administration of the selective D2antagonist eticlopride (0.5 mg/kg, s.c.) for 3 weeks produced a selective supersensitivity of both dorsal (caudate‐putamen) and ventral (nucleus accumbens) striatal neurons to the inhibitory effects of the D2agonist quinpirole (applied by microiontophoresis). This treatment also abolished the normal ability of the D1agonist SKF 38393 to potentiate quinpirole‐induced inhibition, and relieved D2receptors from the necessity of D1receptor stimulation by endogenous DA (enabling), as indicated by significant electrophysiological and behavioral (sterotypy) effects of quinpirole in eticlopride‐pretreated, but not saline‐pretreated, rats that were also acutely depleted of DA. Daily administration of the selective D1receptor antagonist SCH 23390 (0.5 mg/kg, s.c.) caused supersensitivity of striatal neurons to the inhibitory effects of SKF 38393 and also abolished both the ability of SKF 38393 to potentiate quinpirole‐induced inhibition and the necessity of D1receptor stimulation for such inhibition. However, both quinpirole‐induced inhibition of striatal cells and stereotyped responses were also somewhat enhanced in SCH 23390‐pretreated rats. When such Dl‐sensitized rats were acutely depleted of DA, the behavioral effects of quinpirole were intermediate between saline‐pretreated rats with acute DA depletion and SCH 23390‐pretreated rats without acute DA depletion. Based upon these and related results, it is argued that the enhanced effects of quinpirole in D1‐sensitized rats are due to a heterologous sensitization of D2receptors rather than to enhanced enabling resulting from supersensitive D1receptors. It is suggested that supersensitivity of either D1or D2receptors can lead to an uncoupling of normal qualitative and quantitative D1/D2synergisms and that the heterologous regulation of D2receptor sensitivity by D1receptors may be related to uncoupling of funct

ISSN:0887-4476    

DOI:10.1002/syn.890170106

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

年代:1994

数据来源: WILEY

摘要:

AbstractAn interaction or link between dopamine D1 receptors and dopamine D2 receptors was found by a ligand competition method, using [3H]raclopride to label dopamine D2 receptors and SCH 23390 to block dopamine D1 receptors. In the presence of endogenous or exogenous dopamine, SCH 23390 increased the binding of [3H]raclopride in post‐mortem human striata homogenates or in tissue culture cells containing human dopamine D1 and D2 receptors. In order to reveal such intramembrane receptor‐receptor interactions in general, therefore, it appears essential to add two agonists, one for each receptor, and then to block one of the receptors when measuring the binding of a ligand to the second receptor. © 1994 Wiley‐Lis

ISSN:0887-4476    

DOI:10.1002/syn.890170107

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

年代:1994

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890170108

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

年代:1994

数据来源: WILEY

ISSN:0887-4476    

DOI:10.1002/syn.890170101

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

年代:1994

数据来源: WILEY