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PubMed2005

Differential effects of endocannabinoids on [(3)H]-GABA uptake in the rat globus pallidus.

In the globus pallidus, cannabinoid CB(1) receptors are localized pre-synaptically on GABAergic neurons. We assessed the influence of the endocannabinoids, anandamide, 2-arachidonoyl-glycerol (2-AG) and noladin ether, on the uptake of [(3)H]-GABA in pallidal slices from rat. Both 2-AG and noladin ether increased [(3)H]-GABA uptake (by 40.8 +/- 8.0% and 38.4 +/- 12.5%). The effect of 2-AG was blocked by the cannabinoid CB(1) receptor antagonist AM 251. In contrast, neither anandamide nor the agonist WIN 55,212-2 had an effect on [(3)H]-GABA uptake. Different roles might be played by different endocannabinoids, both physiologically and in basal ganglia disorders, such as Parkinson's disease.

Animals↗

PubMed2004

HCN2 and HCN1 channels govern the regularity of autonomous pacemaking and synaptic resetting in globus pallidus neurons.

The globus pallidus (GP) is a critical component of the basal ganglia circuitry controlling motor behavior. Dysregulation of GP activity has been implicated in a number of psychomotor disorders, including Parkinson's disease (PD), in which a cardinal feature of the pathophysiology is an alteration in the pattern and synchrony of discharge in GP neurons. Yet the determinants of this activity in GP neurons are poorly understood. To help fill this gap, electrophysiological, molecular, and computational approaches were used to identify and characterize GABAergic GP neurons in tissue slices from rodents. In vitro, GABAergic GP neurons generate a regular, autonomous, single-spike pacemaker activity. Hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels make an important contribution to this process: their blockade with ZD7288 significantly slowed discharge rate and decreased its regularity. HCN currents evoked by somatic voltage clamp had fast and slow components. Single-cell RT-PCR and immunohistochemical approaches revealed robust expression of HCN2 subunits as well as significant levels of HCN1 subunits in GABAergic GP neurons. Transient activation of striatal GABAergic input to GP neurons led to a resetting of rhythmic discharge that was dependent on HCN currents. Simulations suggested that the ability of transient striatal GABAergic input to reset pacemaking was dependent on dendritic HCN2/HCN1 channels. Together, these studies show that HCN channels in GABAergic GP neurons are key determinants of the regularity and rate of pacemaking as well as striatal resetting of this activity, implicating HCN channels in the emergence of synchrony in PD.

Action Potentials↗

PubMed2004

GABAergic neurotransmission in globus pallidus and its involvement in neurologic disorders.

The globus pallidus occupies a critical position in the 'indirect' pathway of the basal ganglia and, as such, plays an important role in the modulation of movement. In recent years, the importance of the globus pallidus in the normal and malfunctioned basal ganglia is emerging. However, the function and operation of various transmitter systems in this nucleus are largely unknown. GABA is the major neurotransmitter involved in the globus pallidus. By means of electrophysiological recording, immunohistochemistry and behavioral studies, new information on the distribution and functions of the GABAergic neurotransmission in the rat globus pallidus has been generated. Morphological studies revealed the existence of GABA(A) receptor, including its benzodiazepine binding site, and GABA(B) receptor in globus pallidus. At subcellular level, GABA(A) receptors are located at the postsynaptic sites of symmetric synapses (putative GABAergic synapses). However, GABA(B) receptors are located at both pre- and postsynaptic sites of symmetric, as well as asymmetric synapses (putative excitatory synapses). Consistent with the morphological results, functional studies showed that activation of GABA(B) receptors in globus pallidus reduces the release of GABA and glutamate by activating presynaptic auto- and heteroreceptors, and hyperpolarizes pallidal neurons by activating postsynaptic receptors. In addition to GABA(B) receptor, activation of GABA(A) receptor benzodiazepine binding site and blockade of GABA uptake change the activity of globus pallidus by prolonging the duration of GABA current. In agreement with the in vitro effect, activation of GABA(B) receptor, GABA(A) receptor benzodiazepine binding site and blockade of GABA uptake cause rotation in behaving animal. Furthermore, the GABA system in the globus pallidus is involved in the etiology of Parkinson's disease and regulation of seizures threshold. It has been demonstrated that the abnormal hypoactivity and synchronized rhythmic discharge of globus pallidus neurons associate with akinesia and resting tremor in parkinsonism. Recent electrophysiological and behavioral studies indicated that the new anti-epileptic drug, tiagabine, is functional in globus pallidus, which may present more information to understand the involvement of globus pallidus in epilepsy.

Animals↗

PubMed1976

The striatal efferents in the globus pallidus and in the substantia nigra.

The radial fibers in the globus pallidus are the striatal efferents. Evidence now indicates that they arise from medium-sized neurons in the striatum. During their transit of the globus pallidus, they give off collaterals in both segments of the globus pallidus and undergo reduction in caliber. It has not been possible to observe the same radial fiber emitting collaterals in both segments of the globus pallidus, and the prospects of ever doing so are not good. The radial fibers in the medial segment of the globus pallidus continue into the substantia nigra by way of the "comb" bundle. The divergence and convergence in the striatal efferent systems is considerable. The afferent plexuses of fine fibers bearing bouton en passant endings, which completely ensheath the long dendrites in the globus pallidus and the substantia nigra and make "longitudinal axodendritic connections," are derived from the convergence of branches off the collaterals of a number of different radial fibers in the globus pallidus and the convergence of "comb" bundle fibers in the substantia nigra. The synaptic endings on these fibers constitute most of the endings in the globus pallidus. They are the endings with large, egg-shaped, synaptic vesicles and form symmetrical synapses.

Animals↗

PubMed2002

Rotational behavior and electrophysiological effects induced by GABA(B) receptor activation in rat globus pallidus.

GABA is the major neurotransmitter used in the globus pallidus and there is evidence that GABA(B) receptors exist in this nucleus. Here we show that unilateral microinjection of baclofen, a GABA(B) receptor agonist, induced ipsilateral turning in Sprague-Dawley rats. This effect was prevented by preinjection of the GABA(B) receptor antagonist CGP55845A, which itself did not cause rotation. Thus, activation of GABA(B) receptor may suppress the activity of globus pallidus neurons, which is in line with the finding that the glutamate receptor antagonists (+/-)-2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione also caused similar ipsilateral turning when injected into globus pallidus. Furthermore, in the presence of these glutamate receptor antagonists, injection of baclofen resulted in fewer rotations. To test the possibility that baclofen reduced glutamate release onto globus pallidus neurons, the effects of baclofen on miniature excitatory postsynaptic currents were studied in rat brain slices. Patch-clamp recordings showed that baclofen at 30 microM significantly reduced the frequency of the miniature excitatory postsynaptic currents. However, baclofen induced a weak outward current only in a minority of globus pallidus neurons. These pre- and postsynaptic effects of baclofen were reversed or prevented by CGP55845A. These results suggest that GABA(B) receptor in globus pallidus plays an important role in the regulation of movement by modulating glutamatergic inputs at a presynaptic site.

Animals↗

PubMed1988

Synaptic organization of the globus pallidus.

The synaptic organization of the globus pallidus is reviewed with respect to present knowledge about neurons, fibers, axon terminals, and their intrinsic synaptic relationships. Information derived from studies employing Nissl stains, Golgi impregnations, lesion degeneration techniques, immunohistochemistry, and anterograde axonal labeling in various species are presented along with ultrastructural data. Studies indicate that the globus pallidus contains a principal efferent neuron with smooth or spiny dendrites and simple or complex terminal dendritic arborizations. This cell type receives convergent inputs from intrinsic and extrinsic sources and uses gamma-aminobutyric acid as a transmitter. A smaller and separate population of pallidal projection neurons contains acetylcholine. Two other less frequent neuronal types, of small and medium size, have also been recognized. Three to six types of axonal boutons forming synaptic contacts with pallidal neurons have been recognized in various studies. Among these, three types (types I, II, and III) are the most prevalent. Studies indicate that the most frequent category (type I) originates from neostriatal neurons via radial fiber projections and contains immunoreactive GABA and enkephalins. The synaptic architecture of the globus pallidus is dominated by a mosaic-like arrangement of long dendrites that are ensheathed by longitudinally oriented axons making synapses en passant. Triadic synapses involving dendrites that are pre- and postsynaptic are encountered infrequently. Because both striatopallidal and pallidothalamic connections are inhibitory, pallidal target neurons in the thalamus may be "disinhibited" when the neostriatum is activated.

Animals↗

PubMed2001

The role of the globus pallidus D2 subfamily of dopamine receptors in pallidal immediate early gene expression.

The globus pallidus plays an important role in basal ganglia circuitry, representing the first relay nucleus of the 'indirect pathway' of striatal efferents. In contrast to the well-characterized actions of dopamine on striatal neurons, the functional role of the dopamine innervation of globus pallidus is less well understood. Previous research showed that systemic administration of either a dopamine D2 receptor antagonist or combined dopamine D1 and D2 receptor agonists induces Fos, the protein product of the immediate early gene c-fos, in neurons of globus pallidus [Ruskin and Marshall (1997) Neuroscience 81, 79-92]. To determine whether the ability of the D2 receptor antagonist, sulpiride, to induce Fos in rat pallidal neurons is mediated by D2-like receptors in striatum or globus pallidus, intrastriatal or intrapallidal sulpiride infusions were conducted. The diffusion of intrastriatal sulpiride was estimated by measuring this antagonist's competition for N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)-induced D2 receptor inactivation. The phenotype of the striatal neurons expressing Fos after intrastriatal infusion was assessed by combining Fos immunocytochemistry with D2 receptor mRNA in situ hybridization. Intrastriatal infusions of (-)-sulpiride (10-200 ng) dose-dependently increased the number of striatal cells expressing Fos; and the Fos-immunoreactive striatal cells were D2 receptor mRNA-expressing, the same population in which systemic D2 receptor antagonists induce Fos. Intrastriatal infusions of high (5 microg), but not low (10-200 ng), (-)-sulpiride doses also induced Fos in globus pallidus cells but the sulpiride appeared to spread to the globus pallidus. Direct intrapallidal infusions of (-)-sulpiride (50-100 ng) dose-dependently induced Fos in globus pallidus with minimal influence on striatum or other basal ganglia structures. Using sensitive in situ hybridization conditions, prominent labeling of D2 receptor mRNA was evident in globus pallidus. D2 receptor mRNA was densest in a lateral 200 microm wide band that follows the curvature of the pallidal/striatal boundary. Cellular analysis revealed silver clusters associated with D2 receptor mRNA labeling over globus pallidus neurons that were immunoreactive for neuron-specific nuclear protein. These results strongly suggest that the dopaminergic innervation of globus pallidus, acting through D2-like receptors internal to this structure, can control gene expression in pallidal neurons.

Animals↗

PubMed1978

Baclofen (beta-p-chlorophenyl-gamma-aminobutyric acid) enhances [3H]gamma-aminobutyric acid (3H-GABA) release from rat globus pallidus in vitro.

The rat globus pallidus has been investigated as a possible model in which to study pre-synaptic GABA mechanisms in vitro. (+/-)-Baclofen (300 micrometer-1 mM) significantly enhanced the release of radioactivity from superfused slices of rat globus pallidus prelabelled with 3H-GABA in vitro. This releasing action was specific to the (+)-isomer of baclofen: neither the (-)-isomer nor another neuronal depressant dl-alpha-epsilon-diaminopimelic acid had any significant effect. The releasing effect of baclofen appeared unrelated to the phenethylamine moiety of its structure as neither beta-phenethylamine nor dopamine evoked release of 3H-GABA from pallidal slices. Baclofen increased the efflux of radioactivity from pallidal slices prelabelled with either [3H]-beta-alanine or [3H]diaminobutyric acid in vitro. The use of specific glial and neuronal GABA uptake blocking compounds (beta-alanine and (+/-)-cis-1,3-amino-cyclohexanecarboxylic acid) did not permit resolution of the elements from which baclofen was evoking [3H]GABA release. Baclofen also inhibited uptake of [3H]GABA into pallidal slices with an IC50 value of 6 x 10(-4) m. The GABA-like properties of baclofen may be related to the (+)-isomer while non-specific neuronal depressant actions are an effect of the (-)-isomer. The potential of the (+)-isomer as an antipsychotic agent while (-)-baclofen remains the effective antispastic drug free from unwanted side-effects, is discussed.

Alanine↗

PubMed1982

Neostriatal enkephalin-immunoreactive neurones project to the globus pallidus.

The origin of enkephalin-immunoreactive nerve terminals in the globus pallidus was investigated by combining immunocytochemistry with stereotaxic injection of neurotoxic agents (colchicine and kainic acid) and microknife deafferentations. The intracerebral administration of colchicine, irrespective of whether in the caudate putamen or in globus pallidus, induces the appearance of enkephalin-immunoreactive cell bodies and fibres in the caudate putamen. No immunoreactive cell bodies were depicted in the globus pallidus after this treatment. Kainic acid injections in the caudate putamen produced topographic depletions of enkephalin-immunoreactive terminals in the globus pallidus. The more anterior injections produced medial-anterior depletions, while posterior injections gave latero-posterior depletions. Injections in the globus pallidus produced only a non-specific loss of fluorescence restricted to the tip of the cannula. Coronal microknife cuts produced a combination of build-up and depletion of enkephalin immunofluorescence according to the position of the cut. The build-up of immunoreactive materials was always observed in the caudate-putamen side of the cut while depletions observed in the globus pallidus were related to the extent of deafferentation of this nucleus from the caudate putamen. All these observations confirmed the neostriatal origin (caudate putamen) of the enkephalinergic fibres present in the paleostriatum (globus pallidus).

Animals↗

PubMed1980

Projections of the feline globus pallidus.

The organization of globus pallidus (GP) projections was studied in cats using autoradiographic and horseradish peroxidase (HRP) techniques. Both methods confirmed the existence of a topographically organized projection to subthalamic nucleus (STN). Although all but the most caudal GP projects to STN, the heaviest projection is to the lateral two-thirds. In addition, HRP studies showed that the GP projection to the medial part of substantia nigra, pars reticulata receives projections from the rostral lateral GP, while lateral substantia nigra receives input from caudal GP. There is in addition a small projection from caudal GP to the caudal lateral mesencephalon. This most caudal projection of GP arises from the portion of GP which projects the least to the subthalamic nucleus. Mesencephalic and pontine cells labeled after injection of horseradish peroxidase into STN were in areas receiving projections from GP and entopeduncular nucleus, suggesting there may be reciprocal relationships between these areas. Labeled cells were located in the lateral part of subthalamic nucleus after injection into the lateral portion of substantia nigra pars reticulata, but cells were not labeled after medial injection. Pontine injections of HRP also revealed that cells in fields of Forel and zona incerta project to pons but very few subthalamic nucleus cells project there.

Amygdala↗

PubMed1981

Diffuse enkephalin innervation from caudate to globus pallidus.

The source of enkephalin in neuronal terminals of the rat globus pallidus was evaluated with electrolytic and knife cut lesions. Straight knife cuts medial to the globus pallidus or a curved knife cut just below the corpus callosum do not reduce immunofluorescence staining in the globus pallidus, indicating that cerebral cortex is not a major source of pallidal enkephalin. Electrolytic lesions of dorsal and ventral portions of the globus pallidus, and even lesions which sever medial from lateral globus, fail to reduce pallidal staining, ruling out long enkephalin neurons traversing the globus. Large electrolytic lesions of the head of the caudate do decrease dorsal pallidal fluorescence, though multiple small caudate lesions are without observable effect. Large pallidal lesions elicit a build-up of enkephalin fluorescence in the caudate. These results suggest that the caudate is the sole source of pallidal enkephalin and that the innervation diffusely converges on the smaller globus pallidus.

Animals↗

PubMed2004

Hyperintense globus pallidus on T1-weighted MR imaging in acute kernicterus: is it common or rare?

Globus pallidus involvement is a well-known magnetic resonance (MR) imaging finding of acute kernicterus. However, it is not clear how early the involvement of globus pallidus occurs and whether or not it is seen in every case. Therefore, we aimed to investigate the globus pallidus involvement in 13 neonates with acute kernicterus by MR imaging. Thirteen neonates who were admitted with jaundice, encephalopathy and indirect hyperbilirubinemia (mean, 37.0 mg/dl) were prospectively evaluated with cranial MR imaging. Pathological signal changes were noted concerning the globus pallidus. Eight of the 13 patients demonstrated bilateral, symmetric increased signal intensity in the globus pallidus on T1-weighted MR imaging. These lesions were not apparent on T2-weighted images. Multiple parenchymal punctuate T1 hyperintense lesions were detected in one patient without globus pallidus involvement. This appearance was consistent with hemorrhage. The MR imaging findings of the other four patients showed no evidence of abnormality. The symmetric involvement of globus pallidus seen as hyperintense on T1-weighted MR imaging is a common and characteristic finding of acute kernicterus.

Acute Disease↗

PubMed1975

The radial fibers in the globus pallidus.

In our Golgi collection of adult monkey brains the striatal efferents, i.e., the radial fibers in the globus pallidus and the "comb" bundle fibers in the internal capsule and in the cerebral peduncle, are well impregnated in the horizontally sectioned brain and in a sagittal sectioned brain. Since collaterals emerging from radial fibers are seen only in the horizontal series and not in the saggittal series, the interpretation is that they proceed anteriorly and posteriorly only, following the curvature of the pallidal segments, and do not run superiorly or inferiorly as they emerge. Although radial fibers emitting collaterals in the lateral segment and in the medial segment of the globus pallidus have been observed, it has not been possible to observe the same radial fiber emitting collaterals in both pallidal segments and the prospects of ever doing so are not good. The radial fibers converging in the globus pallidus pursue many radii and there is little coincidence between the plane of section and the planes in which they travel. At most only severed radial fiber segments 100-150 microns in length can be found in the horizontal sections needed to observe the collaterals. Moreover, sagittal sections trodorsally, as they pass through the internal medullary lamina to enter the medial segment of the globus pallidus. The radial fibers in the medial segment of the globus pallidus are continuous with the "comb" bundle fibers and appear to be thinner than the radial fibers in the lateral segment of the globus pallidus. It is not proved; nonetheless, the view expressed here is that the radial fibers are thinner in the medial segment of the globus pallidus because they may be the same fibers that gave off collaterals in the lateral segment of the globus pallidus. This is discussed in the light of the electrophysiological disclosure of Yoshida et al. ('71, '72) that caudatopallidal fibers are collaterals off caudatonigral fibers. The afferent plexuses of fine, "bouton en passage" fibers, which completely ensheath the long radiating dendrites in the globus pallidus (Fox et al., '66) are well impregnated in the horizontal series. Obviously, they are formed by a number of ultimate branches converging from the collateral brances of a number of different radial fibers. The divergence, too, in this system must be considerable; however, its true extent can only be surmised from the several radial fibers and radial fiber collaterals seen in the incompletely impregnanted Golgi section. Continued.

Animals↗

PubMed1994

Neurochemical compartmentalization of the globus pallidus in the rat: an immunocytochemical study of calcium-binding proteins.

The globus pallidus external segment forms a major target center of the mammalian striatum which is characterized by neurochemically distinct compartments. The present study was undertaken to determine if a corresponding compartmentalization exists within the globus pallidus external segment in the rat. Immunocytochemical examination of the calcium-binding proteins parvalbumin and calbindin D28kDa, which are present in neurons of the striatal matrix compartment, was employed. The results indicate three neurochemically distinct compartments within the globus pallidus external segment: 1) an area in the medial aspect of the entire length of the globus pallidus that contains dense immunoreactivity for calbindin D28kDa; 2) a narrow rim at the striatopallidal junction in the rostral two-thirds of the globus palidus that contains calbindin D28kDa immunoreactivity designated as the "border zone" of the globus pallidus; and 3) an area between these two zones showing very poor immunoreactivity for calbindin D28kDa but containing parvalbumin immunoreactive neurons. The calbindin D28kDa immunoreactive border zone corresponds to the area of the globus pallidus where striatal inputs converge extensively, whereas the rest of the nucleus is involved in segregated, topographically organized pathways. Parvalbumin-containing neurons are involved in the propagation of striatal output related to striosomal and sensorimotor aspects of basal ganglia function. The present results also indicate that calbindin D28kDa immunoreactivity is completely absent from striosomal neurons and is therefore a useful marker for striatal compartments.

Animals↗

PubMed1999

Synergistic influences of the striatum and the globus pallidus on postural and locomotor control.

We have investigated the role of the globus pallidus in locomotor and postural control in a previously established animal model of striatal dysfunction. Striatal efferent activity was suppressed by intracerebral infusions of antisense oligodeoxynucleotides targeted to the messenger RNA of the proto-oncogene, c-fos. This suppression produced robust circling behavior and an atypical expression of c-fos in the ipsilateral globus pallidus following psychostimulant challenge. Simultaneous infusions of antisense oligodeoxynucleotides into both the caudate-putamen and the ipsilateral globus pallidus produced an approximate threefold increase in the intensity of rotation elicited by D-amphetamine. Excitotoxic lesioning of the globus pallidus produced marked postural asymmetry and circling behavior upon stimulation. The intensity of this rotational behavior was similar to that produced by dual infusions of antisense oligodeoxynucleotides into the caudate-putamen and the globus pallidus, and was not further potentiated by suppression of striatal c-fos expression. These results demonstrate the importance of the globus pallidus in postural and motor control, and suggest that activation of this nucleus through a reduction in striatopallidal inhibition may function to balance the output activity of the basal ganglia.

Animals↗

PubMed1996

[Activity and function of neurons in the globus pallidus in Parkinson's disease].

We investigated the activity and functional distribution of globus pallidus neurons in Parkinson's disease patients and recorded single cell activity of globus pallidus medialis and changes related to the movements of different joints in 31 patients during stereotactic ventral pallidotomy procedure. We showed that discharge rates of 19% of medial globus pallidus neurons were modulated by passive contralateral movements; 77.2% of these pallidal units showed changes related solely to single joint movement and 22.8% showed different patterns of activity in relation to two and more joints. We also identified somatotopically arranged cell clusters that alter the discharge rate with related movements; oro-facial movement-related cells in caudo-ventral region and, leg-related cells in dorso-rostral part and arm-related cells between these two parts of medial globus pallidus. These findings suggest a partial somatotopic organization of human globus pallidus medialis.

Action Potentials↗

PubMed1988

Deoxyglucose analysis of the specific topographic functional interrelations between substantia nigra and globus pallidus.

The response of the ipsilateral globus pallidus (GP) to unilateral electrical stimulation of the substantia nigra reticulata (SNr) was studied in the rat, by the autoradiographic [14C]-deoxyglucose method. Different compartments within the GP were metabolically activated, depending on the localization of the electrically stimulated subregions within the SNr. Computer generated, quantified colour coded glucograms were used for the analysis of specific topographic organization of the pallido-nigral functional system. Stimulation of the medial or lateral segments within the SNr induced activation in the medial or lateral compartments of the GP, respectively. Stimulation of the dorsal or ventral subregions within the SNr elicited activation in the ventral or dorsal compartments of the GP, respectively. Activation of the medial or lateral GP compartments was independent of stimulation in the dorsal or ventral SNr segments and vice versa. These results suggest that the topographic interrelations between the substantia nigra and the globus pallidus are characterized by preservation of the mediolateral and inversion of the dorsoventral functional correspondence. The neuronal territory involved into this topographic organization is suggested to consist of the subthalamic and striatal nerve cells projecting collateral axons to both the SNr and the GP.

Animals↗

PubMed2003

Effects of the GABA-uptake inhibitor tiagabine in rat globus pallidus.

To elucidate the cellular action of tiagabine, an inhibitor of GAT-1 GABA transporter, in the globus pallidus, whole-cell patch-clamp recordings were made from rat globus pallidus neurons in the acutely prepared brain slice. Superfusion of tiagabine significantly prolonged the decay kinetics of both action potential-dependent and -independent (tetrodotoxin-resistant) inhibitory postsynaptic currents (IPSCs) that were mediated by GABA(A) receptors. Furthermore, it decreased the frequency of these IPSCs. The latter effect was reversed by the GABA(B) receptor antagonist CGP55845, which alone had no effect, suggesting the involvement of presynaptic GABA(B) receptors. Thus, tiagabine could inhibit or disinhibit globus pallidus neurons by increasing the activation of the GABA(A) receptors and presynaptic GABA(B) receptors, respectively. In the behaving animal, tiagabine when injected unilaterally into the globus pallidus caused consistent ipsilateral rotation of the rats indicative of increased inhibition of globus pallidus activity. This finding could be explained by the proposition that in the presence of tiagabine, prolonged action of GABA on GABA receptors would dominate over the inhibitory effect of tiagabine on GABA release. Our findings on the electrophysiological and behavioral effects of tiagabine in globus pallidus suggest that this basal ganglia nucleus is one of the sites of action of tiagabine and provides a rationale for investigating its involvement in epilepsy.

Animals↗