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T Antonelli

Publications and source records attributed to T Antonelli.

At least 37 records · Page 2Linked to original sources
PubMed2000

Nicotinic modulation of [(3)H]D-aspartate outflow from cultured cerebellar granule cells.

The effect of nicotine on basal and electrically evoked (20 Hz for 20 sec) [(3)H]D-aspartate efflux (assumed as an index of transmitter release) was studied in rat cerebellar granule primary cultures. Nicotine (10-100 nM) increased the basal efflux two to three times and concentration-dependently enhanced the electrically evoked efflux up to ten times. Higher drug concentration (1 microM) underwent rapid desensitization. Facilitation of the efflux was similarly reduced by the nicotinic acetylcholine receptor antagonists, alpha-bungarotoxin and mecamylamine, suggesting the involvement of at least two receptor subtypes containing and lacking alpha(7) subunits, respectively. Since the increased efflux induced by nicotine in granule cells kept at rest or depolarized by KCl 15 mM was antagonized by tetrodotoxin, the involvement of sodium channels by receptors located at preterminal sites was suggested. Taken together, these findings emphasize the role of the cholinergic input in granule cell function and in glutamatergic signaling.

Acetylcholine↗
PubMed2000

Neurotensin increases endogenous glutamate release in rat cortical slices.

In the present study, the effects of the tridecapeptide neurotensin [NT(1-13)] and its fragments, NT(1-7) and NT(8-13), on endogenous glutamate release from rat cortical slices, were evaluated. NT(1-13) (100-1000 nM) slightly increased spontaneous glutamate release, while it was ineffective at 1 and 10 nM concentrations. Neither the biologically active NT fragment NT(8-13) nor the inactive one NT(1-7) affected basal glutamate release. NT(1-13) (1-1000 nM) enhanced potassium (35 mM)-evoked glutamate release displaying a bell-shaped concentration response curve. In addition NT(8-13) (10 nM) increased K+-evoked-glutamate release similarly to the parent peptide (10 nM), while the biologically inactive fragment NT(1-7) (10-100 nM) was ineffective. The effects of NT(1-13) and NT(8-13) were fully counteracted by the selective neurotensin receptor antagonist SR48692 (100 nM). These findings suggest that NT plays a role in regulating cortical glutamate transmission.

Animals↗
PubMed2000

The nicotinic modulation of [(3)H]D-aspartate outflow in primary cultures of rat neocortical neurons: effect of acute and long term nicotine treatment.

The effect of nicotine 1 nM-10 microM on the efflux of [(3)H]D-aspartate was tested in primary cultures of rat cortical neurons kept at rest and subjected to electrical field stimulation. Two trains of pulses at 20 Hz for 20 s were applied at the 60th (St(1)) and 90th (St(2)) min of perfusion. The drug slightly and transiently increased the efflux of resting cells while, when given during St(2), it greatly enhanced the electrically evoked efflux estimated as St(2)/St(1) ratio, EC(50) being 107 nM. The nicotinic receptors (nAChR) giving rise to this positive modulation were partly mecamylamine- and partly alpha-bungarotoxin-sensitive. They appeared to be located at the nerve endings since nicotine facilitation was only slightly prevented by tetrodotoxin during depolarisation with 15 mM KCl. Pretreatment with glutamate antagonists did not reveal any interaction between nAChR and ionotropic glutamate receptors. Membrane glutamate carrier involvement in the nicotine effect was ruled out. Long-term treatment with nicotine 1 microM (from the 3rd-4th to the 8th-9th day in vitro) reduced the maximal response to the drug but shifted its threshold concentration to the left (from 10 nM to 1 nM), leaving the contribution of the two receptor subtypes unchanged. Reduced responsiveness to nicotine was also evident in long-term treated cerebellar granule cells. In conclusion, presynaptic nAChR's, both containing and lacking alpha(7) subunits, can contribute to enhance the glutamatergic secretion in primary cultures of rat cortical neurons, chiefly during electrical stimulation.

Acetylcholine↗
PubMed1999

A stereological study on the neuroprotective actions of acute modafinil treatment on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced nigral lesions of the male black mouse.

The effect of an acute administration of the vigilance-promoting drug modafinil ((+/-)(diphenyl-methyl)-sulfinyl-2 acetamide; Modiodal) on the nigrostriatal dopamine system was studied after damage induced by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) by means of immunohistochemistry for tyrosine hydroxylase (TH) and a stereological method. MPTP (40 mg/kg) reduced from 24,380 +/- 902 to 13,501 +/- 522 and from 37,868 +/- 3300 to 20,568 +/- 1270, respectively, the number of TH immunoreactive (IR) and non-TH IR nigral neurons. Co-administration of Modafinil restored to normal the number of these neuronal populations. MPTP treatment induced also a reduction in the volume of TH IR neurons, which was counteracted by Modafinil administration. The data provide morphological evidence, based on unbiased stereological analysis, for a potential neuroprotective role of Modafinil, not only in dopaminergic neurons, but also with a similar magnitude in the non-DA nerve cell population of the substantia nigra after MPTP lesion. These results suggest that Modafinil has a neuroprotective role in the substantia nigra via a still undefined mechanism in which a crucial role of DA uptake blockade should be excluded. Modafinil may therefore have a therapeutic potential in neurodegenerative processes such as those occurring in Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1999

The vigilance promoting drug modafinil increases extracellular glutamate levels in the medial preoptic area and the posterior hypothalamus of the conscious rat: prevention by local GABAA receptor blockade.

The effects of modafinil on glutamatergic and GABAergic transmission in the rat medial preoptic area (MPA) and posterior hypothalamus (PH), are analysed. Modafinil (30-300 mg/kg) increased glutamate and decreased GABA levels in the MPA and PH. Local perfusion with the GABAA agonist muscimol (10 microM), reduced, while the GABAA antagonist bicuculline (1 microM and 10 microM) increased glutamate levels. The modafinil (100 mg/kg)-induced increase of glutamate levels was antagonized by local perfusion with bicuculline (1 microM). When glutamate levels were increased by the local perfusion with the glutamate uptake inhibitor L-trans-PDC (0.5 mM), modafinil produced an additional enhancement of glutamate levels. Modafinil (1-33 microM) failed to affect [3H]glutamate uptake in hypothalamic synaptosomes and slices. These findings show that modafinil increases glutamate and decreases GABA levels in MPA and PH. The evidence that bicuculline counteracts the modafinil-induced increase of glutamate levels strengthens the evidence for an inhibitory GABA/glutamate interaction in the above regions controlling the sleep-wakefulness cycle.

Amino Acids↗
PubMed1998

Modafinil prevents glutamate cytotoxicity in cultured cortical neurons.

The ability of modafinil (Modiodal) to protect cortical neurons from glutamate-induced degeneration was evaluated by measuring electrically evoked [3H]GABA release and [3H]GABA uptake in primary cerebral cortical cultures. In normal cells, electrical stimulation (10 Hz, 2 min) increased [3H]GABA release (FR-NER St1 = 0.77+/-0.14; St2/St1 ratio = 0.94+/-0.02). The exposure of sister cells to glutamate, reduced electrically evoked [3H]GABA release (FR-NER St1 = 0.40+/-0.05; St2/St1 ratio = 0.60+/-0.08). Modafinil (0.3-1 microM) prevented the glutamate-induced reduction of the St2/St1 ratio (0.85+/-0.11; 0.88+/-0.05, respectively). A similar protective effect was observed for [3H]GABA uptake. These findings suggest that modafinil may be neuroprotective in that it attenuates glutamate-induced excitotoxicity in cortical neurons.

Animals↗
PubMed1998

The effects of modafinil on striatal, pallidal and nigral GABA and glutamate release in the conscious rat: evidence for a preferential inhibition of striato-pallidal GABA transmission.

The effects of the anti-narcoleptic drug modafinil (30-300 mg/kg i.p.) on GABA and glutamate release were evaluated in the basal ganglia of the conscious rat, by using the microdialysis technique. Modafinil (100 mg/kg) inhibited striatal (85+/-4% of basal values) and pallidal (85+/-2%) GABA release without influencing local glutamate release. At the highest dose (300 mg/kg), modafinil induced a further reduction of pallidal (75+/-2%) but not striatal (82+/-7%) GABA release and increased striatal (134+/-11%) but not pallidal glutamate release. On the contrary, in the substantia nigra modafinil reduced GABA release only at the 300 mg/kg dose (59+/-5%) without affecting glutamate release. The preferential reduction in striato-pallidal GABA release at the 100 mg/kg dose of modafinil suggests that modafinil may be useful in the treatment of Parkinsonian diseases.

Animals↗
PubMed1998

The striatal neurotensin receptor modulates striatal and pallidal glutamate and GABA release: functional evidence for a pallidal glutamate-GABA interaction via the pallidal-subthalamic nucleus loop.

In the present study, we used dual-probe microdialysis to investigate the effects of intrastriatal perfusion with neurotensin (NT) on striatal and pallidal glutamate and GABA release. The role of the pallidal GABAA receptor in the intrastriatal NT-induced increase in pallidal glutamate release was also investigated. Intrastriatal NT (100 and 300 nM) increased striatal glutamate and GABA (100 nM, 155 +/- 9 and 141 +/- 6%, respectively; 300 nM, 179 +/- 8 and 166 +/- 11%, respectively) release, as well as pallidal glutamate and GABA (100 nM, 144 +/- 8 and 130 +/- 5%; 300 nM, 169 +/- 9 and 157 +/- 8%, respectively) release. These effects were dose-dependently antagonized by the NT receptor antagonist 2-[(1-(7-chloro-4-quinolinyl)-5-(2, 6-dimethoxy-phenyl)pyrazol-3-yl)carboxylamino]tricyclo)3.3.1 .1.3. 7)-decan-2-carboxylic acid (SR48692). Intrasubthalamic injection of the GABAA receptor antagonist (-)-bicuculline (10 pmol/100 nl, 30 sec) rapidly increased pallidal glutamate release, whereas the intrastriatal NT-induced increase in pallidal glutamate release was counteracted by intrapallidal perfusion with (-)-bicuculline, suggesting that an increase in striopallidal GABA-mediated inhibition of the GABAergic pallidal-subthalamic pathway results in an increased glutamatergic drive in the subthalamic-pallidal pathway. These results demonstrate a tonic pallidal GABA-mediated inhibition of excitatory subthalamic-pallidal neurons and strengthen the evidence for a functional role of NT in the regulation of glutamate and GABA transmission in the basal ganglia. The ability of intrastriatal SR48692 to counteract the NT-induced increase in both striatal and pallidal glutamate and GABA release suggests that blockade of the striatal NT receptor may represent a possible new therapeutic strategy in the treatment of those hypokinetic disorders implicated in disorders of the indirect pathway mediating motor inhibition.

Animals↗
PubMed1998

Electrically evoked [3H]GABA release from cerebral cortical cultures: an in vitro approach for studying glutamate-induced neurotoxicity.

In the present study the [3H]GABA release in the rat cerebral cortex primary cultures, kept at rest or electrically stimulated, was measured. In addition, the development of excitotoxic cell damage caused by pretreating the cells for 10 min with increasing glutamate concentrations (10-300 microM) was examined 2 and 24 h after the insult. Cellular injury was quantitatively assessed by measuring the electrically-evoked [3H] GABA release, the [3H] GABA uptake, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide staining. Trains of electrical pulses at different frequencies (2, 5, 10, and 20 Hz) applied to the cultures elicited a [3H]GABA release which was frequency related, Ca++-dependent, and tetrodotoxin sensitive. Either 2 or 24 h after glutamate exposure, the electrically evoked [3H]GABA release was reduced by glutamate in a concentration dependent manner, while [3H]GABA uptake and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide staining appeared less sensitive. The N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and metabotropic receptor antagonists were tested on 100 microM glutamate-exposed cells and a prominent N-methyl-D-aspartate receptor-mediated component was observed. The present findings indicate that the electrically-evoked [3H]GABA release from cerebral cortical cells could represent a useful approach not only to study the spike-triggered neurosecretion but also to the neuronal damage caused by glutamate, as well as to test potential neuroprotective compounds.

Analysis of Variance↗
PubMed1998

Protective effect of GV150526A on the glutamate-induced changes in basal and electrically-stimulated cytosolic Ca++ in primary cultured cerebral cortical cells.

Glutamate-induced changes in intracellular free Ca++ concentration ([Ca++]i) were recorded in resting and electrically-stimulated primary cultures of rat cerebral cortical cells, employing the Ca++ indicator Fura 2. A brief (10 min) exposure to glutamate led to a concentration-dependent basal [Ca++]i increase, measured 30 min after glutamate removal. In order to unmask more subtle modifications in [Ca++]i movements associated with neurosecretion, the glutamate effect was also studied in electrically-stimulated cells. The application of trains (10 s) of electrical pulses (intensity 30 mA, duration 1 ms) induced frequency-related Na+- and Ca++-dependent [Ca++]i transients. A 5 min treatment with 50 microM glutamate reduced to 48% the electrically-evoked [Ca++]i transients, evaluated 30 min after glutamate challenge. The neuroprotective effect of sodium 4,6-dichloro-3-[(E)-3-(N-phenyl)propenamide]indole-2-carboxylate (GV150526A), a new indole derivative with high affinity and selectivity for the glycine site of the NMDA receptor-channel complex, was compared with that of DL-2-amino-5-phosphonopentanoic acid (AP5), ifenprodil, 7-chlorokynurenic acid and 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)-quinoxaline (NBQX) on glutamate-induced [Ca++]i changes in resting and electrically-stimulated cells. In both experimental conditions, GV150526A showed to be the most potent compound. Moreover, GV150526A and 7-chlorokynurenic acid were 2-3 times more active in stimulated neurons than in resting neurons, indicating a major involvement of the glycine site in the protection of the cells kept in an active state.

Animals↗
PubMed1998

Differential mechanisms in the effects of disulfiram and diethyldithiocarbamate intoxication on striatal release and vesicular transport of glutamate.

Intoxication with the alcohol-aversive drug disulfiram (Antabuse) and related dithiocarbamates may provoke neuropathies and, in some cases, damage the basal ganglia. Rats received a single administration of disulfiram (7 and 500 mg kg-1 i.p.) and equimolar doses (4 and 290 mg kg-1 i.p.) of its metabolite diethyldithiocarbamate (DDC), roughly corresponding to the daily maximum dose in alcohol abusers or to an estimated nonlethal overdose, respectively. The striatal, extracellular levels of glutamate in freely moving rats previously implanted with a microdialysis probe increased after low and intoxicating doses of disulfiram (126 +/- 3% and 154 +/- 10% of basal values, respectively) and DDC as well (135 +/- 10% and 215 +/- 14%, respectively), a partially Ca++-dependent effect. The prolonged (>7 hr) disulfiram-induced increase in glutamate observed in vivo may reflect the in vitro disulfiram-evoked release of glutamate from striato-cortical synaptic vesicles, where the drug nonspecifically inhibited (Ki approximately 4 microM) the uptake function and abolished the transmembrane proton gradient (DeltapH). In contrast, DDC did not seem to affect DeltapH. The prompt DDC-provoked increase in extracellular levels of glutamate was prevented by 7-nitroindazole, an in vivo specific inhibitor of neuronal nitric oxide synthase, which suggests that the thiol metabolite also acts via the nitric oxide synthesis. At variance, the short-acting 7-nitroindazole did not prevent the sustained in vivo effects of disulfiram and of DDC putatively formed with time. These findings provide new evidence for differential mechanisms underlying disulfiram- and DDC-induced increases in striatal glutamate release. Present glutamatergic changes, although not appearing dramatic enough to represent the only cause for neuronal damage from disulfiram overdose, might contribute to the drug neurotoxicity.

Alcohol Deterrents↗
PubMed1997

The antinarcoleptic drug modafinil increases glutamate release in thalamic areas and hippocampus.

The antinarcoleptic drug modafinil [(diphenyl-methyl)-sulfinyl-2-acetamide; Modiodal] dose-dependently inhibits the activity of GABA neurons in the cerebral cortex and in the nucleus accumbens, as well as in sleep-related brain areas such as the medial preoptic area and the posterior hypothalamus. This study examined the effects of modafinil (30-300 mg/kg, i.p.) on dialysate glutamate and GABA levels in the ventromedial (VMT) and ventrolateral (VLT) thalamus and hippocampal formation (Hip) of the awake rat. The results show a maximal increase in glutamate release in these brain regions at the 100 mg/kg dose, associated with a lack of effect on GABA release. Thus modafinil may increase excitatory glutamatergic transmission in these regions, altering the balance between glutamate and GABA transmission.

Animals↗
PubMed1997

The muscarinic modulation of [3H]D-aspartate efflux and [Ca2+]i levels in rat cerebellar granule cells.

The effects of ACh on [3H]D-aspartate efflux and on calcium levels ([Ca2+]i) were studied at the same time in sister cultures of rat cerebellar granule cells stimulated with electrical pulses (5-20 Hz) or depolarized with KCl (15-40 mM). ACh, 0.3-1000 nM, greatly facilitated the 10-Hz-evoked tritium efflux while its effect on 20 mM KCl-evoked efflux was significantly smaller. ACh, 10-1000 nM, enhanced [Ca2+]i levels to a limited extent under both experimental conditions. Therefore, ACh facilitation was evident above all on the electrically evoked [3H]D-aspartate efflux. The ACh-mediated responses depended on the activation of M3-muscarinic receptors since these responses were blocked by 4-DAMP. ACh, 50 microM, reduced the [Ca2+]i plateau, determined by prolonged electrical or KCl stimulation. This effect was due to its action of M2-receptors being blocked by AF-DX 116. In conclusion, at very low concentrations, ACh greatly facilitated the electrically evoked [3H]D-aspartate efflux through M3-receptors, while at a higher concentrations, it inhibited, through M2-receptors, the rise in [Ca2+]i caused by prolonged cell depolarization.

Acetylcholine↗
PubMed1997

Glutamate regulation of dopamine release in guinea pig striatal slices.

The effect of L-glutamic acid (L-Glu) on basal and electrically evoked [3H]-dopamine efflux in guinea pig striatal slices was studied. In the presence of magnesium, L-Glu significantly increased spontaneous [3H]-dopamine efflux. This response was unaffected by the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), the non-competitive NMDA receptor antagonist, D-5-methyl-10,11, dihydro-5-H-dibenzo-[a,d]-cyclohepten-5,10-imine maleate (MK-801), the glycine antagonist 7-chlorokynurenic acid (7-CL-KYN) and by the metabotropic receptor antagonist (+)-alpha-methyl-4-carboxyphenyl-glycine (alpha-M4CPG) and L-2-amino-3-phosphonopropionic acid (L-AP3). However, the metabotropic glutamate receptor agonist, trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD), increased spontaneous [3H]-dopamine efflux, as did L-Glu, and this response was completely counteracted by alpha-M4CPG. In the absence of magnesium, L-Glu induced a concentration-dependent increase in basal [3H]-dopamine efflux, which was prevented by MK-801. In electrically stimulated striatal slices L-Glu, applied 25 min before the stimulation, concentration-dependently increased the [3H]-dopamine efflux both in the presence and in the absence of magnesium. This effect was completely prevented by CNQX, but not by MK-801 or DL-2-amino-5-phosphono-pentanoic acid (AP5). On the contrary, L-Glu, applied during electrical stimulation (2 min) in the absence of Mg2+, increased the [3H]-dopamine efflux to 200%, and this effect was partly counteracted by MK-801. These results provide evidence that different subtypes of excitatory amino acid receptors modulate [3H]-dopamine efflux depending on the functional state (rest or activity) of the nerve endings. The spontaneous [3H]-dopamine efflux appears to be controlled by metabotropic receptors in the presence of Mg2+ and by NMDA receptors in its absence. Conversely, the AMPA/kainate receptors facilitate the electrically evoked [3H]-dopamine efflux in the presence of Mg2+, whereas the NMDA receptors appeared to be operative, in the absence of Mg2+, as long as L-Glu was applied simultaneously with the electrical stimulation.

Animals↗
PubMed1997

Differential effects of intrastriatal neurotensin(1-13) and neurotensin(8-13) on striatal dopamine and pallidal GABA release. A dual-probe microdialysis study in the awake rat.

In the present dual-probe microdialysis study the effects of intrastriatal perfusion with the tridecapeptide neurotensin(1-13) [NT(1-13)] and its active fragment NT(8-13) on striatopallidal GABA and striatal dopamine release were investigated. The modulatory action of NT(1-13) on D2 receptor-mediated inhibition of striatal and pallidal GABA release was also studied. Both intrastriatal NT(1-13) (100 nM) and NT(8-13) (100 nM) increased striatal (139 and 149% respectively) and pallidal (130 and 164%) GABA release, and this effect was antagonized by intrastriatal perfusion with the neurotensin receptor antagonist SR48692 (100 nM). A similar increase (155%) in striatal dopamine release was observed following intrastriatal NT(1-13) (100 nM), but not NT(8-13) (100 and 500 nM). However, at the highest concentration studied (1 microM) NT(8-13) was associated with a rapid increase (130%) in striatal dopamine release. In a second study intrastriatal NT(1-13) (10 nM) counteracted the inhibition of striatal and pallidal GABA release induced by pergolide (500 and 1500 nM). The inhibitory action of the D2 agonist was restored when SR48692 (100 nM) was added to the perfusion medium. These results suggest that in the neostriatum the neurotensin receptor located postsynaptically on the striatopallidal GABA neurons seems to differ from the neurotensin receptor located on dopaminergic terminals, as indicated by the relative lack of effect of NT(8-13) on striatal dopamine release. Furthermore, the ability of NT(1-13) to counteract the pergolide-induced inhibition of both striatal and pallidal GABA release strengthens the evidence for antagonistic receptor-receptor interaction between postsynaptic striatal neurotensin and D2 receptors located on striatopallidal GABA neurons.

Animals↗
PubMed1996

The vigilance promoting drug modafinil decreases GABA release in the medial preoptic area and in the posterior hypothalamus of the awake rat: possible involvement of the serotonergic 5-HT3 receptor.

The effect of modafinil on endogenous gamma-aminobutyric acid (GABA) release in the medial preoptic area (MPA) and posterior hypothalamus (PH) and the role of local 5-HT3 receptors in this effect was investigated in the awake rat using in vivo microdialysis. Modafinil (30-100 mg/kg i.p.) dose-dependently decreased GABA release from the MPA, while only the 100 mg/kg dose markedly reduced GABA release in the PH. The modafinil (100 mg/kg) induced inhibition of GABA release in the MPA and the PH was partially counteracted by the 5-HT3 receptor antagonist MDL72222 (1 microM) when perfused locally alone or together with the non-selective 5-HT receptor antagonist methysergide (1 microM). Thus, the reduction of GABA transmission induced by modafinil in the MPA and in the PH, at least in part, involves local 5-HT3 receptors. The GABA release inhibition by modafinil in the above areas may be relevant for its vigilance promoting action.

Animals↗
PubMed1996

The vigilance promoting drug modafinil increases dopamine release in the rat nucleus accumbens via the involvement of a local GABAergic mechanism.

The present in vivo microdialysis study demonstrated that the subcutaneous injection of modafinil (diphenyl-methyl-sulfinyl-2-acetamide) in doses of 30-300 mg/kg dose dependently increased dopamine release from the intermediate level of the nucleus accumbens along the rostro-caudal axis of the halothane anaesthetized rat. The effect of modafinil in a dose of 100 mg/kg was counteracted by the local perfusion in the nucleus accumbens with the GABAB receptor antagonist phaclofen (beta-p-chlorophenyl-gamma-aminopropyl-phosphonic acid) (50 microM), the GABAA agonist muscimol (3-hydroxy-5-aminomethyl-isoxazolol) (10 microM) and the neuronal GABA reuptake inhibitor SKF89976A (4,4-diphenyl-3-butenyl-nipecotic acid) (0.1 microM), whereas it was increased by the GABAB receptor agonist (-)-baclofen [beta-(p-chlorophenyl-gamma-aminobutyric acid)] (10 microM). In addition, the modafinil-induced increase of dopamine release was associated with a significant reduction of accumbens GABA release. These results suggest that the dopamine releasing action of modafinil in the rat nucleus accumbens is secondary to its ability to reduce local GABAergic transmission, which leads to a reduction of GABAA receptor signaling on the dopamine terminals.

Analysis of Variance↗