Biomedical subjects

G Segovia

Publications and source records attributed to G Segovia.

At least 19 recordsLinked to original sources

PubMed2006

Environmental enrichment reduces the function of D1 dopamine receptors in the prefrontal cortex of the rat.

Environmental enrichment produces changes in spontaneous and psychostimulant-induced motor activity. Dopamine in the prefrontal cortex (PFC), through the activation of D1 receptors, has been suggested to play a role in modulating motor activity. The present study investigated the effects of environmental enrichment on spontaneous motor activity, prefrontal acetylcholine release following local D1 receptor stimulation and D1 receptor expression in the PFC. Male wistar rats (3 months of age) were housed in enriched or isolated conditions during 90 days. Animals were then implanted with guide cannulae to perform microdialysis experiments in the PFC. Spontaneous motor activity and acetylcholine extracellular concentrations were monitored simultaneously. Also spontaneous motor activity was measured in an open field. On completion of the experiments, the density of D1 receptors in the PFC was studied by immunocytochemistry. Rats housed in an enriched environment showed significantly lower spontaneous motor activity in the open field compared to isolated animals. Perfusion of the D1 agonist SKF38393 (50 microM; 40 min) in the PFC produced long lasting increases of spontaneous motor activity and of local dialysate concentrations of acetylcholine in both groups of rats. However, increases of both motor activity and acetylcholine concentrations were significantly lower in enriched compared to isolated animals. Moreover, the density of D1 receptors in the PFC was significantly reduced in animals housed in an enriched environment. These results are the first evidence suggesting that environmental enrichment during adult life changes the function of D1 dopamine receptors in the PFC.

Acetylcholine↗

PubMed2005

Changes in dopamine and acetylcholine in striatum of the awake rat after chronic treatment with a dopamine uptake blocker.

The effects of chronic treatment with a dopamine uptake blocker on dopamine and acetylcholine extracellular concentrations in striatum of the awake rat was studied. Male Wistar rats received daily injections (i.p.) of the dopamine uptake blocker nomifensine (10 mg/kg) during 22 days. Control group was injected with vehicle (saline). Microdialysis experiments were performed on days 1, 8, 15 and 22 of treatment. Nomifensine injections increased extracellular concentration of dopamine in striatum in all days of treatment without differences among days. In contrast, acetylcholine levels showed no changes in days 1 and 8 but increased in days 15 and 22 of treatment. These results shows that chronic treatment with a dopamine uptake inhibitor, nomifensine, has no effects on dopamine release but it increases acetylcholine release in striatum of the awake rat. These results would help to further understand the effects of chronic dopamine uptake inhibition.

Acetylcholine↗

PubMed2003

Effects of activation of NMDA and AMPA glutamate receptors on the extracellular concentrations of dopamine, acetylcholine, and GABA in striatum of the awake rat: a microdialysis study.

The effects of activation of the AMPA and NMDA ionotropic glutamate receptors on the extracellular concentration of dopamine, acetylcholine, (ACh) and GABA in striatum of the awake rat was investigated. Also the levels of DOPAC, HVA, and choline (Ch) were included in this study. Seven to eight days after stereotaxical implantation of a guide-cannulae assembly, microdialysis experiments were performed. The dopamine and ACh content of samples were measured by HPLC coupled to electrochemical detection. GABA was measured using fluorometric detection. Perfusion of AMPA (1, 20, 100 microM) produced a dose-related increase of dopamine and a dose-related decrease of DOPAC and HVA. AMPA 100 microM decreased extracellular concentrations of ACh and increased the extracellular concentration of Ch and GABA. Perfusion of NMDA 500 microM increased the concentration of dopamine and decreased DOPAC and HVA. Also, NMDA 100 microM decreased DOPAC. NMDA 500 microM decreased the extracellular concentrations of ACh and increased the concentrations of Ch and GABA. Perfusion of the AMPA/kainate-antagonist DNQX (100 microM) blocked the effects of AMPA (100 microM) on dopamine, DOPAC, HVA, ACh, and GABA concentrations. Perfusion of the NMDA-antagonist CPP (100 microM) blocked the effects of NMDA 500 microM on dopamine, DOPAC, HVA, ACh, Ch, and GABA concentrations. These results suggest an interaction between glutamate-dopamine-ACh-GABA in striatum of the awake rat.

Acetylcholine↗

PubMed2003

Changes in dialysate concentrations of glutamate and GABA in the brain: an index of volume transmission mediated actions?

Brain microdialysis has become a frequently used method to study the extracellular concentrations of neurotransmitters in specific areas of the brain. For years, and this is still the case today, dialysate concentrations and hence extracellular concentrations of neurotransmitters have been interpreted as a direct index of the neuronal release of these specific neurotransmitter systems. Although this seems to be the case for neurotransmitters such as dopamine, serotonin and acetylcholine, the extracellular concentrations of glutamate and GABA do not provide a reliable index of their synaptic exocytotic release. However, many microdialysis studies show changes in extracellular concentrations of glutamate and GABA under specific pharmacological and behavioural stimuli that could be interpreted as a consequence of the activation of specific neurochemical circuits. Despite this, we still do not know the origin and physiological significance of these changes of glutamate and GABA in the extracellular space. Here we propose that the changes in dialysate concentrations of these two neurotransmitters found under specific treatments could be an expression of the activity of the neurone-astrocyte unit in specific circuits of the brain. It is further proposed that dialysate changes of glutamate and GABA could be used as an index of volume transmission mediated actions of these two neurotransmitters in the brain. This hypothesis is based firstly on the assumption that the activity of neurones is functionally linked to the activity of astrocytes, which can release glutamate and GABA to the extracellular space; secondly, on the existence of extrasynaptic glutamate and GABA receptors with functional properties different from those of GABA receptors located at the synapse; and thirdly, on the experimental evidence reporting specific electrophysiological and neurochemical effects of glutamate and GABA when their levels are increased in the extracellular space. According to this concept, glutamate and GABA, once released into the extracellular compartment, could diffuse and have long-lasting effects modulating glutamatergic and/or GABAergic neurone-astrocytic networks and their interactions with other neurotransmitter neurone networks in the same areas of the brain.

Animals↗

PubMed2003

Growth hormone and aging.

In elderly people, vascular alterations and degenerative alterations of the Central Nervous System (CNS) are two of the most common reasons for illness and death. Lipid pattern modifications and menopause in women are some of the causes for the appearance of these alterations. Vascular endothelium is in part responsible for vascular homeostasis, through the production of several vasoactive factors. Growth hormone (GH) exerts effects on the CNS and on the vascular endothelium, since GH deficient subjects exhibit endothelium-dependent alterations, which recover under substitutive GH treatment. Growth hormone has important actions on lipid metabolism that also play a role on vascular and endothelial function. Moreover, cardiac function improves when GH is associated to angiotensin II receptor blockers. Elderly people exhibit a physiological GH deficiency that could affect their vascular and cerebral functions. A study was carried out using old Wistar rats to clarify the effects of GH on the vessels under chronic "in vivo" conditions. The response to various vasoactive substances in aortic rings has been evaluated. An increase in the aortic media thickness was seen in old rats, which showed also a reduction in the vasodilator response to isoprenaline as compared to young animals. GH treatment partially restored the vasodilator response and reduced media thickness. Neuronal population was reduced in the hypocampus of old rats as compared to young ones and GH treatment was able to significantly enhance the number. Neurotransmitters were measured in several cerebral areas to establish differences between young and old GH-treated or untreated animals. Glutamine, Arginine and Aspartate were reduced in old animals whereas Citruline was increased. GH treatment restored in all cases the levels corresponding to young rats.

Aged↗

PubMed2001

Dopamine release during stress in the prefrontal cortex of the rat decreases with age.

The effects of aging on the stress-induced increases of dopamine and the dopamine metabolites 3,4-dihydroxyphenylaectic acid (DOPAC) and homovalinic acid (HVA) in the medial prefrontal cortex of the awake rat were investigated using microdialysis. In young rats (2-3 months) handling stress produced an increase of dopamine by 205% and of the dopamine metabolites DOPAC by 120% and HVA by 155% of baseline as maximal increases. In middle-aged rats (14 months) the increase of dopamine was significantly lower than in young rats (155% of baseline), while in aged rats (30 months) stress produced no significant increases of dopamine in the prefrontal cortex. These results indicate that the effects of stress on dopamine release in the medial prefrontal cortex of the rat diminishes during the normal process of aging.

Aging↗

PubMed2001

Endogenous glutamate-taurine interaction in striatum and nucleus accumbens of the freely moving rat: studies during the normal process of aging.

Using microdialysis, the effects of endogenous glutamate on extracellular concentrations of taurine, in striatum and nucleus accumbens of the awake rat during the normal process of aging were investigated. The glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) was perfused through the microdialysis probe to increase the endogenous concentration of glutamate. Young (2-4 months), middle aged (12-14 months), aged (27-32 months) and very aged (37 months) male Wistar rats were used. PDC (1, 2 and 4 mM) produced a dose-related increase of extracellular concentrations of glutamate and taurine in striatum and nucleus accumbens in all groups of age. Increases of glutamate, but not of taurine, decreased during aging in striatum. In nucleus accumbens there were no age-related changes in the increases of glutamate and taurine induced by PDC. In all age groups, increases of extracellular taurine were significantly correlated with increases of extracellular glutamate. However, when these taurine-glutamate correlations for all groups of age were compared, no statistical differences were found. These results show first that a decrease in the increases of glutamate produced by the glutamate reuptake inhibitor in striatum, but not in nucleus accumbens, is produced by age; second that glutamate-taurine interaction in striatum and nucleus accumbens does not change during the normal process of aging.

Aging↗

PubMed2001

Involvement of NMDA and AMPA/kainate receptors in the effects of endogenous glutamate on extracellular concentrations of dopamine and GABA in the nucleus accumbens of the awake rat.

We have investigated the effects of perfusion of the N-methyl-D-aspartate (NMDA) receptor antagonist 3-((R)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA)/kainate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) on the endogenous glutamate-evoked changes of extracellular dopamine and alpha-aminobutyric acid (GABA) in the nucleus accumbens of the awake rat. Local infusion of the glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxilic acid in the nucleus accumbens produced an increase in extracellular concentrations of glutamate, dopamine, and GABA. At the dose of 4 mM, the increase of extracellular glutamate, dopamine, and GABA were 3.73 +/- 0.46 microM (n = 8; p < 0.001), 4.70 +/- 0.92 nM (n = 6; p < 0.001) and 0.36 +/- 0.08 microM (n = 8; p < 0.001), respectively. Perfusion of the NMDA-receptor antagonist CPP attenuated the increases of dopamine by 90% (n = 5; p < 0.001), but enhanced the increases of GABA by 70% (n = 7; p < 0.01). Perfusion of the AMPA-receptor antagonist DNQX did not attenuate the increases of GABA. These results suggest a differential mediation of ionotropic glutamatergic receptors in the actions of endogenous glutamate on extracellular concentration of dopamine and GABA.

Animals↗

PubMed2001

Glutamatergic neurotransmission in aging: a critical perspective.

The effects of aging on glutamate neurotransmission in the brain is reviewed and evaluated. Glutamate is the neurotransmitter in most of the excitatory synapses and appears to be involved in functions such as motor behaviour, cognition and emotion, which alter with age. However, relatively few studies have been conducted to study the relationship between glutamate and aging of the brain. The studies presented here indicate the existence of a number of changes in the glutamatergic system during the normal process of aging. First, an age-related decrease of glutamate content in tissue from cerebral cortex and hippocampus has been reported, although it may be mainly a consequence of changes in metabolic activity rather than glutamatergic neurotransmission. On the other hand, studies in vitro and in vivo have shown no changes in glutamate release during aging. Since glutamate sampled in most of these studies is the result of a balance between release and uptake processes, the lack of changes in glutamate release may be due to compensatory changes in glutamate uptake. In fact, a reduced glutamate uptake capacity, as well as a loss in the number of high affinity glutamate transporters in glutamatergic terminals of aged rats, have been described. However, the most significant and consistent finding is the decrease in the density of glutamatergic NMDA receptors with age. A new perspective, in which glutamate interacts with other neurotransmitters to conform the substrates of specific circuits of the brain and its relevance to aging, is included in this review. In particular, studies from our laboratory suggest the existence of age-related changes in the interaction between glutamate and other neurotransmitters, e.g. dopamine and GABA, which are regionally specific.

Aging↗

PubMed2001

Glutamate-glutamine cycle and aging in striatum of the awake rat: effects of a glutamate transporter blocker.

This study investigated the effects of aging on the actions of a specific glutamate reuptake blocker, L-trans-pyrrolidine-2, 4-dicarboxylic acid (PDC), in extracellular glutamate and glutamine in striatum of the awake rat. Microdialysis experiments were performed on young (2-3 months), middle-aged (12-14 months), aged (27-32 months) and very aged (37 months) male Wistar rats. Local infusion of PDC (1-4 mM) in striatum increased the dialysate concentration of glutamate and decreased dialysate concentration of glutamine in all the age-groups. In young rats, decreases of dialysate glutamine were correlated with increases of dialysate glutamate. The same profile glutamine/glutamate as in young rats was found in middle-aged, aged and very aged rats, which suggests that the action of glutamate on the glutamate-glutamine cycle in striatum of the awake rat is not modified as a consequence of aging. We also found a significant correlation between the increases of glutamate produced by PDC and the basal dialysate concentration of glutamine, a relationship that did show a significant change with age. Although the significance of this latter finding remains to be elucidated, it may be important to understand the changes in glutamate-glutamine cycle during aging.

ATP-Binding Cassette Transporters↗

PubMed2000

Effects of endogenous glutamate on extracellular concentrations of taurine in striatum and nucleus accumbens of the awake rat: involvement of NMDA and AMPA/kainate receptors.

Using microdialysis, the effects of endogenous glutamate on extracellular concentrations of taurine in striatum and nucleus accumbens of the awake rat were investigated. The glutamate uptake inhibitor L-transpyrrolidine-2,4-dicarboxylic acid (PDC) was used to increase the extracellular concentration of glutamate. PDC (1, 2 and 4mM) produced a dose-related increase of extracellular concentrations of glutamate and taurine in striatum and nucleus accumbens. Increases of extracellular taurine were significantly correlated with increases of extracellular glutamate, but not with PDC doses, which suggests that endogenous glutamate produced the observed increases of extracellular taurine in striatum and nucleus accumbens. The role of ionotropic glutamate receptors on the increases of taurine was also studied. In striatum, perfusion of the antagonists of NMDA and AMPA/kainate glutamate receptors attenuated the increases of extracellular taurine. AMPA/ kainate, but not NMDA receptors, also reduced the increases of extracellular taurine in nucleus accumbens. These results suggest that glutamate-taurine interactions exist in striatum and nucleus accumbens of the awake rat.

Animals↗

PubMed2000

Melatonin disrupts circadian rhythms of glutamate and GABA in the neostriatum of the aware rat: a microdialysis study.

The purpose of this study was to investigate possible circadian changes in extracellular concentrations of glutamate (GLU) and gamma-aminobutyric acid (GABA). and the influence of melatonin on the levels of these neurotransmitters in the neostriatum of awake rats using in vivo microdialysis. At the same time, the concentrations of the amino acids taurine (TAU), glutamine (GLN) and arginine (ARG), as well as dopamine (DA) and its metabolites 3, 4-dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA), were measured in the extracellular fluid. When dialysates were collected over a 24-hr period (6 hr dark, 12 hr light, 6 hr dark), both GLU and GABA, without the infusion of melatonin, exhibited statistically significant rhythms, with higher levels of these constituents during the dark and lower levels during the day. Perfusion with melatonin (for 19 consecutive hours) prevented the daytime reductions in both GLU and GABA. Of the amino acids measured in the dialysates collected from the neostriatum of non-perfused rats, only ARG exhibited a significant change during the light:dark cycle; again, lowest concentrations were measured during the day. While melatonin perfusion did not statistically significantly influence neostriatal levels of TAU and ARG, GLN levels continued to drop during the infusion of the indoleamine. Dialysate concentrations of DA, DOPAC and HVA exhibited circadian rhythms which were not influenced by melatonin perfusion. The findings indicate there are differential effects of melatonin on extracellular neurotransmitter concentrations in the neostriatum of the awake rat. The results also suggest that the day:night variations in GLU and GABA may relate to daily changes in endogenous melatonin production, while DA and its metabolites are minimally influenced by this secretory product.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1999

Role of glutamate receptors and glutamate transporters in the regulation of the glutamate-glutamine cycle in the awake rat.

In the present study we investigate the effects of a specific glutamate reuptake blocker, L-trans-pyrrolidine-3,4-dicarboxylic acid (PDC), on extracellular concentrations of glutamine and glutamate in the striatum of the freely moving rat. Intracerebral infusions of PDC (1, 2 and 4 mM) produced a dose-related increase in extracellular concentrations of glutamate and a dose-related decrease in extracellular concentrations of glutamine. These increases in extracellular glutamate and decreases in extracellular glutamine were significantly correlated. To investigate the involvement of ionotropic glutamate receptors in the decreases of extracellular glutamine produced by PDC, N-methyl-D-aspartate (NMDA) receptor antagonist and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptor antagonist were used. Perfusion of the NMDA receptor antagonist blocked the decrease of extracellular glutamine but had no effect on the increase of extracellular glutamate, both produced by PDC. Perfusion of the AMPA/kainate receptor antagonist attenuated the increase of extracellular glutamate and not only blocked the decrease of extracellular glutamine but also produced a significant increase of extracellular glutamine. The results reported in this study suggest that both NMDA and AMPA/kainate glutamatergic receptors are involved in the regulation of extracellular glutamine.

ATP-Binding Cassette Transporters↗

PubMed1999

Endogenous dopamine increases extracellular concentrations of glutamate and GABA in striatum of the freely moving rat: involvement of D1 and D2 dopamine receptors.

Interactions between endogenous dopamine, glutamate, GABA, and taurine were investigated in striatum of the freely moving rat by using microdialysis. Intrastriatal infusions of the selective dopamine uptake inhibitor nomifensine (NMF) were used to increase the endogenous extracellular dopamine. NMF produced a dose-related increase in extracellular dopamine and also increased extracellular concentrations of glutamate, GABA, and taurine. Extracellular increases of dopamine were significantly correlated with extracellular increases of glutamate and GABA, but not taurine. To investigate whether the increased extracellular dopamine produced by NMF was responsible for the concomitant increase of glutamate and GABA, D1, and D2 receptor antagonists were used. Dopamine receptor antagonists D1 (SCH23390) and D2 (sulpiride) significantly attenuated the increases of glutamate and GABA produced by NMF. These data suggest that endogenous dopamine, through both D1 and D2 dopamine receptors, plays a role in releasing glutamate and GABA in striatum of the freely moving rat.

Animals↗

PubMed1999

Effects of aging on the interaction between glutamate, dopamine, and GABA in striatum and nucleus accumbens of the awake rat.

The aim of the present study was to investigate, using microdialysis, the effects of aging on the glutamate/dopamine/GABA interaction in striatum and nucleus accumbens of the awake rat. For that, the effects of an increase of the endogenous concentration of glutamate on the extracellular concentration of dopamine and GABA in striatum and nucleus accumbens of young (2-4 months), middle-aged (12-14 months), aged (27-33 months), and very aged (37 months) male Wistar rats were studied. Endogenous extracellular glutamate was selectively increased by perfusing the glutamate uptake inhibitor L-trans-pyrrolidine-3,4-dicarboxylic acid (PDC) through the microdialysis probe. In young rats, PDC (1, 2, and 4 mM) produced a dose-related increase of dialysate concentrations of glutamate in both striatum and nucleus accumbens. PDC also increased dialysate dopamine and GABA in both structures. These increases were significantly correlated with the increases of glutamate but not with the PDC dose used, which strongly suggests that the increases of dopamine and GABA were produced by glutamate. In striatum, there were no significant differences in the dopamine/glutamate and GABA/glutamate correlations between young and aged rats. This means that the effects of glutamate on dopamine and GABA do not change during aging. On the contrary, in the nucleus accumbens of aged rats, the increases of dopamine, when correlated with the increases of glutamate, were significantly lower than in young rats. Moreover, the ratio of dopamine to glutamate increases at maximal increases of glutamate was negatively correlated with aging. On the contrary, the ratio of GABA to glutamate increases in nucleus accumbens was positively correlated with aging, which suggests that the effects of endogenous glutamate on GABA tend to be higher in the nucleus accumbens of aged rats. The findings of this study suggest that aging changes the interaction between endogenous glutamate, dopamine, and GABA in nucleus accumbens, but not in striatum, of the awake rat.

Aging↗

PubMed1998

Role of nitric oxide in modulating the release of dopamine, glutamate, and GABA in striatum of the freely moving rat.

This study investigated the role of nitric oxide (NO) in modulating the basal and N-methyl-D-aspartate (NMDA)-induced release of dopamine (DA), glutamate (GLU), and gamma-aminobutiric acid (GABA) in striatum of the freely moving rat using microdialysis. Intrastriatal infusion of NMDA (5 mM) for 15 min increased extracellular concentrations of DA, GLU, and GABA. NMDA also decreased extracellular concentrations of DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC), and 4-hydroxy-3-methoxyphenylacetic acid (HVA), and of the GLU and GABA precursor, glutamine (GLN). Perfusion of N-nitroarginine (1-5 mM), an inhibitor of the synthesis of NO, potentiated NMDA-induced increases in extracellular concentrations of DA and attenuated increases of extracellular GLU. NMDA-induced decreases of extracellular concentrations of DOPAC were also attenuated by N-nitroarginine. N-nitroarginine had no effect on NMDA-induced changes of extracellular concentrations of GABA, HVA, and GLN. N-nitroarginine decreased basal concentrations of DOPAC and HVA, and increase basal concentrations of GLN, but had no effect on basal DA, GLU, and GABA. These results suggest a role for NO in modulating the NMDA-induced release of DA and GLU in striatum. They also suggest that NO could be regulating the basal metabolism of DA, GLU, and GABA.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1997

Effects of 4-aminopyridine on extracellular concentrations of glutamate in striatum of the freely moving rat.

4-aminopyridine (4-AP) is a voltage-sensitive K(+)-channel blocker extensively used in in vitro experiments as a depolarizing agent for the release of glutamate (GLU). This research investigated whether 4-AP could be used in in vivo experiments using microdialysis. For that, the effects of 4-AP on the extracellular concentrations of glutamate (GLU), glutamine (GLN), taurine (TAU) and citrulline (CIT) in striatum of the freely moving rat were investigated. The effects of 4-AP were compared with those produced by perfusion with a high K+ (100 mM) medium. Intrastriatal perfusion with 4-AP (1, 5 and 10 mM) produced no effects on extracellular [GLU], [TAU] and [CIT], but decreased extracellular [GLN]. Perfusion with a high K+ (100 mM) medium increased extracellular [GLU] and [TAU], decreased extracellular [GLN], and had no effects on [CIT]. To test whether the lack of effects of 4-AP on extracellular [GLU] was due to GLU uptake mechanisms, 4-AP was perfused after a previous inhibition of GLU uptake with L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC). Under the effects of PDC (1 mM), 4-AP (1 mM) had no effects on extracellular [GLU], [TAU] and [CIT], but decreased extracellular [GLN]. These results show that 4-AP decreased extracellular [GLN] but failed to produce a significant release of GLU in striatum of the freely moving rat. Thus, 4-AP can not be used as a depolarizing agent for stimulating the release of GLU in in vivo studies using microdialysis.

4-Aminopyridine↗

PubMed1997

Endogenous glutamate increases extracellular concentrations of dopamine, GABA, and taurine through NMDA and AMPA/kainate receptors in striatum of the freely moving rat: a microdialysis study.

Interactions between glutamate (Glu), dopamine (DA), GABA, and taurine (Tau) were investigated in striatum of the freely moving rat by using microdialysis. Intrastriatal infusions of the selective Glu uptake inhibitor L-trans-pyrrolidine-3,4-dicarboxylic acid (PDC) were used to increase the endogenous extracellular [Glu]. Correlations between extracellular [Glu] and extracellular [DA], [GABA], and [Tau], and the effects of a selective blockade of ionotropic Glu receptors, were studied. PDC (1, 2, and 4 mM) produced a dose-related increase in extracellular [Glu]. At the highest dose of PDC, [Glu] increased from 1.55 +/- 0.35 to 6.11 +/- 0.88 microM. PDC also increased extracellular [DA], [GABA], and [Tau]. The increasing [Glu] was correlated significantly with increasing [DA], [GABA], and [Tau]. PDC also decreased extracellular concentrations of DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and 4-hydroxy-3-methoxyphenylacetic acid (HVA). Perfusion with the NMDA-receptor antagonist 3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (1 mM) or the AMPA/kainate-receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) (1 mM) attenuated the increases produced by PDC (4 mM) on [DA], [GABA], and [Tau], and decreases in [DOPAC] and [HVA]. DNQX also attenuated the increases in [Glu] induced by PDC. These data show that endogenous Glu plays a role in modulating the extracellular concentrations of DA, GABA, and Tau in striatum of the freely moving rat.

Animals↗