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PubMed1978

Cataleptic and anticataleptic effects of muscimol and gabaculine injected into globus pallidus and substantia nigra, and interactions with haloperidol or benzodiazepines.

Intranigral injection of muscimol induced hyperactivity in rats and antagonized haloperidol-induced catalepsy. Intranigral injection of gabaculine, an inhibitor of GABA transaminase, induced similar effects 5h after injection, when the nigral GABA content was increased 7-fold. On the other hand, injections of muscimol (30 ng) into the globus pallidus potentiated the cataleptic effect of haloperidol, and muscimol alone in high doses (100 and 200 ng) induced catalepsy. Gabaculine also induced catalepsy of medium intensity and potentiated the effect of haloperidol 24h after injection, when GABA was increased in the globus pallidus as well as in the substantia nigra. Injections of muscimol into either the globus pallidus or substantia nigra increased striatal HVA and enhanced haloperidol-induced elevation of HVA. Three benzodiazepines, nitrazepam, diazepam and chlordiazepoxide administered orally, potentiated the effect of muscimol (30 ng) injected into the globus pallidus and induced catalepsy. A similar effect was not obtained with phenobarbital. It is suggested that stimulation of GABA receptor or increase of GABA content in the sustantia nigra antagonize haloperidol-induced catalepsy by activation of nigral dopaminergic system, and that enhancement of pallidal GABA function induces catalepsy by non-dopaminergic mechanisms. Potentiation of haloperidol-induced catalepsy by benzodiazepines may be due to enhancement of GABA-ergic transmission within the globus pallidus.

4-Aminobutyrate Transaminase↗

PubMed2003

Relative involvement of globus pallidus and subthalamic nucleus in the regulation of somatodendritic dopamine release in substantia nigra is dopamine-dependent.

Previously, we have shown that GABA(A) receptors and glutamate receptors in substantia nigra play distinct roles in the regulation of somatodendritic dopamine release. GABAergic input to substantia nigra was found to be the primary determinant of the level of spontaneous somatodendritic dopamine release. In contrast, acute blockade of dopamine receptors by systemic haloperidol administration produced an increase in somatodendritic dopamine release in substantia nigra that was found to be dependent exclusively upon activation of nigral glutamate receptors. The focus of the present study was to identify anatomical structures that may participate in the differential regulation of somatodendritic dopamine release by GABA and glutamate under these two conditions. To this end, we pharmacologically inhibited the activity of either globus pallidus or subthalamic nucleus using microinfusion of the GABA(A) receptor agonist muscimol. The effects of these manipulations on spontaneous efflux of somatodendritic dopamine and on increases in this measure produced by systemic haloperidol administration were determined in ipsilateral substantia nigra using in vivo microdialysis. As observed previously, administration of haloperidol (0.5 mg/kg, i.p.) significantly increased extracellular dopamine in substantia nigra. Microinfusion of muscimol (400 ng/200 nl) into globus pallidus also produced a significant increase in somatodendritic dopamine efflux. When haloperidol was administered systemically in conjunction with microinfusion of muscimol into globus pallidus, an increase in nigral dopamine efflux was observed that was significantly greater than that which was produced singly by muscimol microinfusion into globus pallidus or by systemic haloperidol administration. The additive nature of the increases in somatodendritic dopamine release produced by these two manipulations indicates that independent neural circuitries may be involved. Inactivation of subthalamic nucleus by microinfusion of muscimol (200 ng/100 nl) had no effect on spontaneous somatodendritic dopamine efflux. Muscimol application into subthalamic nucleus, however, completely abolished the stimulatory effect of systemic haloperidol on dendritic dopamine efflux in substantia nigra. The present data extend our previous findings by demonstrating: 1) an important involvement of globus pallidus efferents in the GABAergic regulation of somatodendritic dopamine efflux in substantia nigra under normal conditions and, 2) an emergent predominant role of subthalamic nucleus efferents in the glutamate-dependent increase in somatodendritic dopamine efflux observed after systemic haloperidol administration. Thus, the relative influence of globus pallidus and subthalamic nucleus in the determination of the level of somatodendritic dopamine release in substantia nigra qualitatively varies as a function of dopamine receptor blockade. These findings are relevant to current models of basal ganglia function under both normal and pathological conditions, e.g. Parkinson's disease.

Animals↗

PubMedDate not supplied

[Role of globus pallidus in mechanisms of antiepileptic caudate- cortical effects].

The experiments on rats have shown that striatal electrostimulation influences inhibiting cortex epileptic activity decrease under conditions of globus pallidus destruction. Besides, it is noted that globus pallidus lesion exerts a pronounced antiepileptic effect on development of the neocortical epileptic activity complexes. Globus pallidus stimulation enhanced the neocortex interictal seizure activity and transformed it to ictal discharges. The results are discussed in terms of the role of pale globe in mechanisms of caudate inhibitory action on neocortex epileptic activity.

Animals↗

PubMed1985

D2 dopamine receptors in calf globus pallidus: agonist high- and low-affinity sites not regulated by guanine nucleotide.

By use of the radioligand [3H]spiroperidol, D2 3,4-dihydroxyphenylethylamine (dopamine) receptor binding characteristics were studied in calf globus pallidus and compared with those of neostriatum. Antagonist competition curves were monophasic and revealed similar affinities for neostriatum and globus pallidus, suggesting a uniform receptor population with one affinity state for antagonists. In both regions, competition curves with the agonist dopamine were biphasic, distinguishing a high- and low-agonist-affinity state. In neostriatum and globus pallidus, respectively, 45% and 19% of [3H]spiroperidol binding was displaced with high affinity and the remainder with low affinity. In neostriatum, the addition of 0.4 mM GTP resulted in a partial conversion from high- to low-affinity state with a remaining high-affinity component of 15%. In globus pallidus, dopamine binding was not altered by GTP. The capability of GTP to modulate agonist binding to D2 receptors appears to be dependent on their neuroanatomical localization.

Animals↗

PubMed1978

[Connections between the globus pallidus and putamen and the cerebral cortex].

The results are represented on investigation of the projections of the globus pallidus and putamen on the brain cortical fields. In 17 cats a unilateral electrolytic destruction of the exterior and interior globus pallidus, and in 8 cats--unilateral electrolysis of the putamen were performed. The brains were treated after Nauta--Gygax, Fink--Heimer, Kawamura--Niimi. Direct connections between the external globus pallidus with prepiriformic, orbital (field 43), temporal (fields 20, 22), frontal (field 6), precentral (field 4), postcentral (field 2) cortical areas were revealed, and projections of the putamen on the frontal (field 6), precentral (field 4), postcentral (field 2), orbital (field 43) cortical areas were demonstrated. Less fibres connect the putamen with temporal and parietal areas. No convincing evidence was obtained to demonstrate direct connections of the entopedunctular nucleus with the brain cortex.

Animals↗

PubMed1988

Vesicular localization of immunoreactive [Met5]enkephalin in the globus pallidus.

The distribution of enkephalin immunoreactivity in the neuropil of globus pallidus was analyzed with a quick-freezing, postembedment-staining technique for light and electron microscopic immunocytochemistry. Fluorescence images of ultrathin sections on glass slides, obtained with a silicon-intensified-tube (type) video camera, revealed staining in the form of scattered fluorescent dots, each 200-400 nm in diameter. Colloidal gold staining under the electron microscope was associated with 80- to 100-nm vesicles of average electron density, widely dispersed in the neuropil, with usually one and no more than four vesicles in individual sectioned neuronal processes. Analysis of fluorescence images in paired serial sections of thicknesses varying from 25 to 150 nm proved that the 200- to 400-nm dots of fluorescence came from smaller structures, presumably the 80- to 100-nm vesicles. Enkephalinergic vesicles in the globus pallidus were nearly always found in what appeared to be axons of passage and were only infrequently associated with synaptic profiles.

Animals↗

PubMed2004

Neurotensin depolarizes globus pallidus neurons in rats via neurotensin type-1 receptor.

The globus pallidus is a major component in the indirect pathway of the basal ganglia. There is evidence that neurotensin receptors exist in this nucleus. To determine the electrophysiological effects of neurotensin on pallidal neurons, whole-cell patch-clamp recordings were performed in the acutely prepared brain slices. Under current-clamp recordings, neurotensin at 1 microM depolarized pallidal neurons. Voltage-clamp recordings also showed an inward current induced by neurotensin. The depolarizing effect of neurotensin could be mimicked by the C-terminal fragment, neurotensin (8-13), but not by the N-terminal fragment, neurotensin (1-8). Both SR 142948A, a non-selective neurotensin receptor type-1 and type-2 antagonist, and SR 48692, a selective type-1 receptor antagonist, blocked the depolarizing effect of neurotensin, and which themselves had no effect on membrane potential. Thus, neurotensin type-1 receptors appear to mediate the effect of neurotensin. The depolarization evoked by neurotensin persisted in the presence of tetrodotoxin, ionotropic and metabotropic glutamate and GABA receptor antagonists, indicating that neurotensin excited the pallidal neurons by activating the receptor expressed on the neurons recorded. Current-voltage relationship revealed that both the suppression of a potassium conductance and the activation of a cationic conductance are involved in the neurotensin-induced depolarization. Based on the action of neurotensin in the globus pallidus we hypothesize that alterations of the striatopallidal neurotensin system contribute to symptoms of basal ganglia motor disorders.

Action Potentials↗

PubMed1994

Subthalamic nucleus and globus pallidus lesions alter activity in nigrothalamic neurons in rats.

Lesions of the subthalamic nucleus or the globus pallidus altered the response of substantia nigra pars reticulata neurons (antidromically identified as projecting to the thalamus) to electrical stimulation of the frontal agranular cortex. In intact animals, cortical stimulation evokes three independent responses (excitation, inhibition, excitation) that may occur singly or in various combinations. The independence of the various responses, especially the temporally coincident excitatory and inhibitory responses, suggests that the net inhibitory and excitatory pathways carrying these signals from the cortex may converge to varying degrees on individual nigrothalamic neurons. Subthalamic lesions increased total response duration (from 28.4 to 39.7 ms), increased the duration of inhibition (from 18 to 30 ms), decreased the occurrence of excitatory responses, and decreased the intensity of the second excitation (from 1.1 to 0.6 spikes/s). Lesion of the globus pallidus also increased total response duration (up to 38 ms), but by increasing the duration of the second excitation (from 15.1 up to 23.8 ms). The intensity of the second excitation (from 1.1 to 1.5 spikes/stimulus) and the number of cells showing the first and second excitations also increased. The incidence, but not the duration, of the inhibition increased. The mean firing rate increased after subthalamic nucleus lesion (34.2 spikes/s) as compared to intact (27.0) or globus pallidus lesion (25.6). These changes may reflect changes in the relative contribution of the five different pathways transmitting information from the cortex to the substantia nigra. In all cases the cortico-striato-nigral pathway is largely intact.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Hallervorden-Spatz disease: cysteine accumulation and cysteine dioxygenase deficiency in the globus pallidus.

We describe neurochemical abnormalities found in the brains of 2 patients with autopsy-confirmed Hallervorden-Spatz (HS) disease. In 1 patient, contents of cystine and of glutathione-cysteine mixed disulfide in the globus pallidus were markedly elevated above values for appropriate control subjects. Activity of cysteine dioxygenase, which converts cysteine to cysteine sulfinic acid, was reduced in the globus pallidus, but normal in the frontal cortex and putamen of both patients. gamma-Aminobutyric acid content was markedly decreased in the globus pallidus and substantia nigra of both patients. These results suggest that cysteine accumulates locally in the globus pallidus in Hallervorden-Spatz disease as a result of an enzymatic block in the metabolic pathway from cysteine to taurine. Accumulated cysteine may chelate iron, accounting for the local increase in iron content in Hallervorden-Spatz disease. The combined excess of cysteine and ferrous iron may generate free radicals that damage neuronal membranes to cause the typical morphological changes observed in this disorder.

Adult↗

PubMed2004

Hypertrophy of medial globus pallidus and substantia nigra reticulata in 6-hydroxydopamine-lesioned rats treated with L-DOPA: implication for L-DOPA-induced dyskinesia in Parkinson's disease.

The medial globus pallidus plays a crucial role in generation of L-DOPA-induced dyskinesia in patients with Parkinson's disease. The 6-hydroxydopamine-lesioned rat exhibiting behavioral sensitization to L-DOPA is one useful animal model for examining L-DOPA-induced dyskinesia. To determine neuropathological abnormality responsible for behavioral sensitization, the medial globus pallidus and the substantia nigra reticulata in 6-hydroxydopamine-lesioned rats treated with L-DOPA were examined. Intermittent L-DOPA treatment induced hypertrophy of the lesioned-side of medial globus pallidus and substantia nigra reticulata of 6-hydroxydopamine-lesioned rats with behavioral sensitization to L-DOPA. Additionally, coadministration of a 5-HT1A receptor agonist, 8-hydroxy-2(di-n-propylamino)tetralin with L-DOPA, alleviated the hypertrophy with improvement of the behavioral sensitization. These results suggest that hypertrophy of the medial globus pallidus and substantia nigra reticulata is associated with induction of behavioral sensitization to L-DOPA in 6-hydroxydopamine-lesioned rats. Therefore, neuropathological changes corresponding to hypertrophy might underlie L-DOPA-induced dyskinesia in patients with Parkinson's disease.

Animals↗

PubMed2002

Influence of nitric oxide on the spontaneous activity of globus pallidus neurones in the rat.

Previous observations have suggested a role for nitric oxide in the activity of the globus pallidus, but this functional involvement has not yet been tested in vivo. The extracellular activity of single units of the globus pallidus was recorded, and neuronal nitric oxide synthase was inhibited by systemically administering 7-nitro-indazole to a group of anaesthetised rats. Forty-five per cent of cells responded with a decrease in the firing rate. In another group of rats, the microiontophoretic administration of 3-morpholino-sydnonimin-hydrochloride (a nitric oxide donor) induced an increase in neuronal firing rate (24/28 cells), whereas the administration of N-omega-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor) reduced the activity of pallidal neurones (8/11 cells). No electrophysiological differences between drug-sensitive and -insensitive neurones were evidenced. An excitatory role of nitric oxide in controlling the level of spontaneous activity of globus pallidus neurones is suggested, without any influence upon the discharge pattern.

Action Potentials↗

PubMed1990

Fetal striatal neurons grafted into the ibotenate lesioned adult striatum: efferent projections and synaptic contacts in the host globus pallidus.

The efferent projections to the host brain from intrastriatal grafts have been examined at the ultrastructural level. Cell suspensions of E14 rat fetal striatal tissue were implanted into the ibotenic acid lesioned caudate-putamen of adult rats. After survival times of at least five months, the anterograde neuronal tracer Phaseolus vulgaris leucoagglutinin was injected into the grafts. Consistent with our previous light microscopical analysis, anterogradely labelled fibres could be followed from the grafts into the host globus pallidus along the normal trajectory of the striatopallidal pathway in the internal capsule, and a few fibres also reached the entopeduncular nucleus and the substantia nigra. In the electron microscope, the graft-derived efferents were seen to be myelinated as they projected caudally along the fibre bundles of the internal capsule, and they were thus similar to the neostriatal projection in normal control animals. In the host globus pallidus, the graft-derived fibres ramified into a terminal network forming morphologically normal synaptic contacts with neuronal elements in the host globus pallidus. A total of 118 synaptic contacts were identified, all of them formed symmetric membrane specializations. The major postsynaptic targets were dendritic shafts (90%), with only a few contacts with spines or small shafts (8%) and perikarya (2%). The morphology of the synaptic contacts and their distribution on different postsynaptic targets were similar to that which was found in the globus pallidus after tracer-injections into the caudate-putamen of normal control animals. The results show that grafted fetal striatal neurons can grow along the myelinated territory of the internal capsule to reinstate a seemingly normal synaptic input to the previously denervated neurons in the host globus pallidus.

Animals↗

PubMed1992

The striatum and the globus pallidus send convergent synaptic inputs onto single cells in the entopeduncular nucleus of the rat: a double anterograde labelling study combined with postembedding immunocytochemistry for GABA.

The entopeduncular nucleus is one of the major output stations of the basal ganglia. In order to better understand the role of this structure in information flow through the basal ganglia, experiments have been performed in the rat to examine the chemical nature, morphology, and synaptology of the projections from the globus pallidus and striatum to the entopeduncular nucleus. In order to examine the morphology and synaptology of pallidoentopeduncular terminals and striatoentopeduncular terminals, rats were subjected to a double anterograde labelling study. The globus pallidus was injected with Phaseolus vulgaris-leucoagglutinin (PHA-L), and on the same side of the brain, the striatum was injected with biocytin. The entopeduncular nuclei of these animals were then examined for anterogradely labelled pallidal and striatal terminals. Rich plexuses of PHA-L-labelled pallidal terminals and biocytin-labelled striatal terminals were identified throughout the entopeduncular nucleus. At the electron microscopic level, the pallidal boutons were classified as two types. The majority (Type 1), were large boutons that formed symmetrical synapses with the dendrites and perikarya of neurones in the entopeduncular nucleus. Type 2 PHA-L-labelled terminals were much rarer, slightly smaller, and formed asymmetrical synapses. It is suggested that the Type 2 boutons are not derived from the globus pallidus but from the subthalamic nucleus. The biocytin-labelled terminals from the striatum had the typical morphological features of striatal terminals and formed symmetrical synapses. The distribution of the postsynaptic targets of the pallidal terminals and the striatal terminals differed in that the pallidal terminals preferentially made synaptic contact with the more proximal regions of the neurones in the entopeduncular nucleus, whereas the striatal terminals were located more distally on the dendritic trees. Examination in the electron microscope of areas where there was an overlap of the two sets of anterogradely labelled boutons revealed that terminals from the globus pallidus and the striatum made convergent synaptic contact with the perikarya and dendrites of individual neurones in the entopeduncular nucleus. In order to examine the chemical nature of the input to the entopeduncular nucleus from the globus pallidus and the striatum, ultrathin sections were immunostained by the postembedding method to reveal endogenous GABA. Three classes of GABA-containing terminals were identified; two of them formed symmetrical synapses and one rare type formed asymmetrical synapses. The combination of the GABA immunocytochemistry and anterograde labelling revealed that both the striatal and pallidal afferents that make symmetrical synapses with neurones in the entopeduncular nucleus, including those involved in convergent inputs, are GABAergic.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

On the role of enkephalin cotransmission in the GABAergic striatal efferents to the globus pallidus.

In the MPTP-treated primate model of Parkinson's disease, loss of dopaminergic afferents to the striatum leads to increased activity in striatal efferents to the external segment of the globus pallidus. This pathway utilizes both GABA and enkephalin as cotransmitters. Little is known regarding either the role of this cotransmission in the generation of parkinsonian symptoms or of the nature of any functional interaction between GABA and enkephalin. We have investigated the roles played by enkephalin and GABA in mediating parkinsonian symptoms by injection the GABAA antagonist bicuculline and the broad spectrum opioid antagonist naloxone directly into the globus pallidus in the reserpine-treated rat model of parkinsonism. Injections of bicuculline, but not naloxone, had marked antiparkinsonian effects. However, naloxone attenuated the antiparkinsonian effects of bicuculline. We interpret these findings as suggesting that increased GABAergic transmission in the globus pallidus is responsible for the generation of parkinsonian symptoms in the reserpine-treated rat. However, overactive enkephalinergic transmission is not responsible for the generation of symptoms and appears to act to reduce the effects of increased GABAergic transmission. In complementary studies in vitro, we have demonstrated a potential mechanism for this negative interaction. Met-enkephalin (3-10 microM) reduced depolarization-evoked release of GABA from terminals in slices prepared from rat globus pallidus (IC50, 0.38 microM). A better comprehension of the mechanisms by which enkephalin and other peptides modulate the action of amino acid transmitters in the basal ganglia is critical to the understanding of the neural processes underlying basal ganglia function and movement disorders.

Animals↗

PubMed1990

The effects of striatal lesion on turning behavior and globus pallidus single unit response to dopamine agonist administration.

In normal rats, globus pallidus neurons are excited by the systemic administration of postsynaptically active doses of apomorphine. The role of the striatum in mediating this phenomenon was examined by investigating the effects of apomorphine on neuronal activity in the globus pallidus and on turning behavior in rats with unilateral quinolinic acid lesions of the striatum. The lesion markedly reduced striatal choline acetyltransferase activity and GABA content and significantly attenuated apomorphine's effect on the activity of pallidal neurons. Both the extent of attenuation of the electrophysiological response of pallidal neurons in lesioned animals and the neurotoxin-induced decreases in choline acetyltransferase activity and GABA content in the caudal striatum were correlated with the degree of apomorphine-induced turning. The data indicate that striatopallidal neurons contribute to apomorphine's excitatory effect on the activity of pallidal neurons in normal animals.

Animals↗

PubMed1991

Convergence of synaptic inputs from the striatum and the globus pallidus onto identified nigrocollicular cells in the rat: a double anterograde labelling study.

Two major sources of afferent synaptic inputs to projection neurons in the rat substantia nigra reticulata are the striatum and the globus pallidus. In order to understand better the functional relationships between these two afferents in the control of the activity of nigrofugal neurons, experiments have been performed to test the possibility that single nigrofugal cells receive convergent synaptic inputs from the striatum and the globus pallidus. To address this question we have used two different approaches. First, we have developed a double anterograde labelling technique suitable for both light and electron microscopy and combined this procedure with the retrograde transport of lectin-conjugated horseradish peroxidase in order to retrogradely label the nigrocollicular cells. Second, we have combined the anterograde transport of Phaseolus vulgaris-leucoagglutinin from the globus pallidus and immunocytochemistry for DARPP-32 as a marker for the striatal terminals, with the retrograde transport of lectin-conjugated horseradish peroxidase from the superior colliculus. In the double anterograde labelling experiment, biocytin was injected in the striatum, Phaseolus vulgaris-leucoagglutinin in the globus pallidus and lectin-conjugated horseradish peroxidase in the superior colliculus. Following these injections, rich plexuses of biocytin- and Phaseolus vulgaris-leucoagglutinin-labelled terminals were found in the ventral two-thirds of the substantia nigra. The biocytin-positive terminals (striatonigral) were generally small and formed rich plexuses without any apparent neuronal association whereas the Phaseolus vulgaris-leucoagglutinin-labelled terminals (pallidonigral) were much larger and formed baskets around the perikarya of retrogradely and non retrogradely labelled cells in the substantia nigra reticulata. In areas of the substantia nigra reticulata where the fields of biocytin- and Phaseolus vulgaris-leucoagglutinin-labelled terminals overlapped, the perikarya and the proximal dendrites of retrogradely and non retrogradely labelled cells were found to be apposed by numerous Phaseolus vulgaris-leucoagglutinin-immunoreactive pallidonigral terminals and a few biocytin-labelled striatonigral terminals. In the sections prepared for electron microscopy, the biocytin was localized using 3,3'-diaminobenzidine tetrahydrochloride whereas Phaseolus vulgaris-leucoagglutinin was localized using benzidine dihydrochloride. It was thus possible to distinguish the biocytin- from the Phaseolus vulgaris-leucoagglutinin-labelled terminals in the electron microscope by the texture of the reaction product associated with them.4+ Examination of 231 biocytin-labelled (striatonigral) terminals and 105 Phaseolus vulgaris-leucoagglutinin-immunoreactive (pallidronigral) terminals revealed that the striatonigral terminals were generally small, contained few mitochondria and formed symmetric synapses predominantly with the distal dendrites (77%) and far less frequently with the perikarya (3%) of substantia nigra reticulata cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

PubMed2001

Cocaine or selective block of dopamine transporters influences multisecond oscillations in firing rate in the globus pallidus.

Previous studies have shown that direct-acting dopamine agonists modulate the multisecond oscillations which are present in globus pallidus spike trains in vivo in awake rats. To investigate possible modulation by endogenous dopamine and by other monoamines, and by drugs with abuse potential, cocaine or selective monoamine uptake blockers were injected systemically during extracellular recording of single globus pallidus neurons and the results analyzed with spectral and wavelet methods. Both cocaine and the selective dopamine uptake blocker GBR-12909 significantly shortened the period of multisecond oscillations, as well as increasing overall firing rate. Cocaine effects were blocked by dopamine antagonist pretreatment, as well as by N-methyl-D-aspartate receptor antagonist (MK-801) pretreatment. Desipramine and fluoxetine (blockers of norepinephrine and serotonin uptake, respectively) had no significant effects on multisecond oscillations. The results suggest that dopamine has a primary role among monoamines in modulating multisecond oscillations in globus pallidus activity, and that tonic dopaminergic and glutamatergic transmission is necessary for normal slow oscillatory function.

Action Potentials↗

PubMed1996

Synergistic effect of D1 and D2 dopamine receptors on AP-1 DNA-binding activity in the striatum and globus pallidus of the rat with a unilateral 6-OHDA lesion of the medical forebrain bundle.

The synergistic effect of D1 and D2 dopamine receptors on transcription factor AP-1 was studied in the striatum and globus pallidus of rats with unilateral 6-OHDA lesions of the medial forebrain bundle. Contralateral rotational behavior in response to a challenge dose of D1 agonist with and without D2 agonist was determined by behavioral observation, and AP-1 induction was studied by a gel mobility-shift assay. Single administration of vehicle and of a low dose of the D1 agonist (SKF38393, 0.5 mg/kg, i.p.) failed to induce rotational behavior, while the D2 agonists bromocriptine (2.5 mg/kg, i.p.) and quinpirole (1 mg/kg. i.p.) induced low rate rotations. High dose of SKF38393, 10 mg/kg, i.p., and low dose D1 and D2 agonists administered together induced a higher rate of rotation. The gel mobility-shift assay also suggested a synergistic interaction between D1 and D2 receptors on AP-1 induction in both the striatum and globus pallidus ipsilateral to the 6-OHDA lesioned nigrostriatal pathway. However, the mode of AP-1 induction via each dopamine receptor subtype appeared to differ between these brain structures. Thus, in the striatum of the lesioned side, single administration of a high dose of D1 agonist, and combined administration of D1 agonist with either of the D2 agonists resulted in AP-1 induction, while in the globus pallidus, AP-1 binding was induced by the D2 agonist bromocriptine and combined administration of a low dose D1 agonist with D2 agonists, but not by D1 agonist alone, even at a high dose. These results demonstrate that a D1/D2 dopamine receptor synergism is involved is the induction of AP-1 both in the striatum and globus pallidus of the rat with ipsilateral dopamine depletion. The induction of AP-1 via each receptor subtype appears, however, to be differently regulated in these two structures.

Animals↗