Effects of motivational and emotional factors on glutamate release in the nucleus accumbens of rats during feeding

Food intake was shown to decrease the glutamate extracellular level in the nucleus accumbens in both deprived and non-deprived Spraque-Dawly rats. Feeding combined with presentation of a tone previously paired with foot shock caused an increase in the glutamate extracellular level in deprived rats only, whereas the tone alone had no effect. The data suggest that emotional and motivational variations exert co-operative effect on the glutamate release in the nucleus accumbens during feeding.     

Conditioned reflex dopamine release in the nucleus accumbens in rats with disrupted hippocampal formation

Lesion of the hippocampal formation affects in different ways the dopamine release in response to the two phases of emotional conditioning: increases the acquisition and exerts no effect on the expression of the reflex in rats.     

Glutamatergic regulation of citrulline extracellular level in the nucleus accumbens during acquisition and expression of conditioned emotional response

In Spregue-Dawley rats, by means of in vivo microdialysis combined with HPLC analysis, it was shown that acquisition and expression of conditioned emotional response increased extracellular level of citrulline: a nitric oxide coproduct, in the nucleus accumbens. Intraaccumbal infusion of MK-801 (100 microM): an NMDA antagonist, markedly attenuated the increase in extracellular citrulline in the n. accumbens produced by acquisition of the response, and completely prevented its conditioned rise observed during expression of the response. The data obtained suggest that, during acquisition and expression of the conditioned emotional response, glutamatergic input to the n. accumbens might act via NMDA receptors to stimulate NO production within this brain area.     

NO-synthase dependent increase in citrulline extracellular level in the nucleus accumbens during acquisition and expression of conditioned emotional response

In Sprague-Dawley rats, by means of in vivo microdialysis combined with HPLC analysis, it was shown that acquisition and expression of conditioned emotional response resulted in increase in extracellular level of citrulline: a nitric oxide co-product, in the nucleus accumbens. The rise extracellular citrulline caused by the acquisition of the response was significantly reduced by intraaccumbens infusion of 7-nitroindasole (0.5 mM), a selective inhibitor of neuronal NO-synthase, and completely prevented by intraaccumbens infusion of N-nitroarginine (0.5 mM): a nonselective NO-synthase inhibitor. The increase in citrulline extracellular level cased by expression of the conditioned emotional response is completely prevented by infusion of both NO-synthase inhibitors. The data obtained suggest that the acquisition and the expression of the conditioned emotional response increase the production of nitric oxide in the n. accumbens, predominantly due to activation of the neuronal NO-synthase.     

Vesicular and nonvesicular glutamate release in the nucleus accumbens during a forced switch in behavioral strategy

By means of in vivo microdialysis combined with HPLC analysis, we have shown that glutamate extracellular level in the rat n. accumbens increases during a forced switch in behavioral strategy. When infused in the n. accumbens, a Na+ channel blocker tetrodotoxin (TTX, 1 microM) completely prevents this increase whereas a potent cystine/glutamate exchanger blocker (S)-4-carboxyphenylglycine ((S)-4-CPG, 5 microM) has no effect. In contrast, TT (1 microM), infused in the n. accumbens, fails to significantly alter basal level of extracellular glutamate in this region whereas (S)-4-CPG (5 microM) produced a significant decrease. Our data suggest that basal and factional glutamate releases in the n. accumbens are differently regulated. The source of basal glutamate release is a non-vesicular release via cystine/glutamate exchanger. Functional glutamate release observed during a forced switch in behavioral strategy derives from vesicular synaptic pool.     

Changes in glutamate release in the rat nucleus accumbens during food and pain reinforcement

In vivo microdialysis combined with HPLC-EC analysis was used to monitor extracellular glutamate in the n. accumbens of Sprague-Dawley rats during footshock and food delivery. The footshock presentation resulted in a delayed increase in extracellular glutamate level, whereas the food intake caused its decrease. The intra-accumbens infusion of glutamate reuptake blocker D,L-threo-beta-hydroxiaspartate (1 mM) completely prevented the food-induced decrease in glutamate level. The intra-accumbens infusion of sodium channel blocker tetrodotoxin (1 microM) led to an increase in glutamate extracellular level in the n. accumbens in response to food intake. The results suggest that the food-induced decrease in glutamate extracellular level in the n. accumbens occurs due to an enhancement of high-affinity glutamate uptake that is probably under the neuronal control during feeding.     

Inhibition of non-vesicular glutamate release by group III metabotropic glutamate receptors in the nucleus accumbens

Previous in vitro studies have shown that group III metabotropic glutamate receptors (mGluRs) regulate synaptic glutamate release. The present study used microdialysis to characterize this regulation in vivo in rat nucleus accumbens. Reverse dialysis of the group III mGluR agonist l-(+)-2-amino-4-phosphonobutyric acid (L-AP4) decreased, whereas the antagonist (R,S)-alpha-methylserine-O-phosphate (MSOP) increased the extracellular level of glutamate. The decrease by L-AP4 or the increase by MSOP was antagonized by co-administration of MSOP or L-AP4, respectively. Activation of mGluR4a by (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid or mGluR6 by 2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric acid had no effect on extracellular glutamate. (R,S)-4-Phosphonophenylglycine (PPG), another group III agonist with high affinity for mGluR4/6/8, reduced extracellular glutamate only at high concentrations capable of binding to mGluR7. The increase in extracellular glutamate by MSOP was tetrodotoxin-independent, and resistant to both the L-type and N-type Ca2+ channel blockers. L-AP4 failed to block 30 mm K+-induced vesicular glutamate release. Blockade of glutamate uptake by d,l-threo-beta-benzyloxyaspartate caused a Ca2+-independent elevation in extracellular glutamate that was reversed by L-AP4. Finally, (S)-4-carboxyphenylglycine, an inhibitor of cystine-glutamate antiporters, attenuated the L-AP4-induced reduction in extracellular glutamate. Together, these data indicate that group III mGluRs regulate in vivo extracellular glutamate in the nucleus accumbens by inhibiting non-vesicular glutamate release.     

Citrulline extracellular level in the nucleus accumbens during acquisition and extinction of classical conditioned fear response with pain reinforcement

By means of in vivo microdialysis combined with HPLC analysis, we have shown that extracellular levels of citrulline (NO co-product) and arginine (NO precursor) increase in the rat n. accumbens during acquisition and expression of a classical fear response. The conditioned rise of citrulline and arginine levels gradually decreased in the course of extinction. The renewal of the response produced an increase in extracellular citrulline and arginine levels. These data suggest that the acquisition of conditioned fear response causes an increase in NO production in the n. accumbens that weakens during the extinction and is restored during the reinstatement of the response.     

D1 dopamine receptors regulate citrulline extracellular level in the nucleus accumbens during expression of conditioned fear response

In rats, expression of conditioned fear response increased extracellular level of citrulline in the nucleus accumbens. Infusion of SCH-23390 into the nucleus accumbens exerted no long-term effect on the baseline citrulline level but attenuated the increase in the extracellar citrulline produced by the expression of the response. The data obtained suggest that, during the expression of the conditioned fear response, the dopaminergic input to the n. accumbens might act via D1 receptors to stimulate NO production within this brain area.     

β-Lactam antibiotic produces a sustained reduction in extracellular glutamate in the nucleus accumbens of rats

We investigated the short- and long-term effects of ceftriaxone on glutamate transporter subtype 1 (GLT-1) transporter activity and extracellular glutamate in the rat nucleus accumbens. Repeated ceftriaxone administration (50, 100 or 200 mg/kg, i.p.) produced a dose-dependent reduction in glutamate levels that persisted for 20 days following discontinuation of drug exposure. The ceftriaxone effect was prevented by the GLT-1 transporter inhibitor dihydrokainate (1 μM, intra-accumbal). These results suggest that β-lactam antibiotics produce an enduring reduction in glutamatergic transmission in the brain reward center.     

Nociceptin differentially affects morphine-induced dopamine release from the nucleus accumbens and nucleus caudate in rats

The effects induced by nociceptin on morphine-induced release of dopamine (DA), 3,4-dihydroxyphenilacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens and nucleus caudate were studied in rats by microdialysis with electrochemical detection. Nociceptin administered intracerebroventricularly (i.c.v.) at doses of 2, 5 and 10 nmol/rat changed neither DA nor metabolites release in the shell of the nucleus accumbens or in the nucleus caudate. Morphine administered intraperitoneally (i.p.) (2, 5, and 10 mg/kg) increased DA and metabolites release more in the shell of the nucleus accumbens than in the nucleus caudate. When nociceptin (5 or 10 nmol) was administered 15 min before morphine (5 or 10 mg/kg), it significantly reduced morphine-induced DA and metabolites release in the shell of the nucleus accumbens, whereas only a slight, nonsignificant reduction was observed in the nucleus caudate. Our data indicate that nociceptin may regulate the stimulating action associated with morphine-induced DA release more in the nucleus accumbens than in the nucleus caudate, and are consistent with recent observations that nociceptin reversed ethanol- and morphine-induced conditioned place preference. Therefore, the nociceptin-induced reduction of DA release stimulated by morphine in the nucleus accumbens, and the results obtained with nociceptin in the conditioned place preference procedure suggest a role for nociceptin in the modulation of the behavioral and neurochemical effects of abuse drugs.     

Dopamine-dependent inhibition of glycine release in the rat nucleus accumbens during feeding

Food intake decreased the glycine extracellular level in the rat n.accumbens. Tetrodotoxin prevented the decrease, whereas D,L-threo-beta-hydroxyaspartic acid exerted no effect. Raclopride (D2 dopamine receptor antagonist) increased the glycine extracellular level in food intake. The data obtained suggest that during feeding the glycine release in the n.accumbens is controlled by the D2 dopamine receptors.     

Tetrodotoxine-dependent glycine release in the rat nucleus accumbens during correction of feeding behaviour

Presence of a tone previously paired with a foot-shock in rats during food intake increases the glycine extracellular level in the n. accumbens. The increase will be completely prevented by intra-accumbal infusion of Na-channel blocking agent tetrodotoxine. The findings suggest that glycine mechanisms in the n. accumbens are involved in the correction of feeding behaviour.     

Evoked potentials during the elaboration of a conditioned reflex to hippocampal stimulation in rats

In experiments on 9 rats, the study of evoked potentials (EPs) of the CA1 field of the dorsal hippocampus to stimulation of its symmetrical part serving as a signal of drinking conditioned reflex (CR) showed that during reflex elaboration, the amplitude of the main EP components significantly decreased; CR did not appear when the population spike (PS) was absent in the hippocampal response. PS always accompanying CR was not specific only of it, it was also recorded at other behavioural reactions. Changes of fascia dentata EPs in the process of CR elaboration to stimulation of its symmetrical part consisted in decrease of the initial negative wave and increase of the positive one. The obtained data point to a significant reconstruction of excitatory and inhibitory inputs to the hippocampus and fascia dentata under the influence of conditioned activity.     

Enhancement of glutamate release in the extracellular space of nucleus accumbens during presentation of aversive or neutral stimuli instead of food reinforcement

By means of in vivo microdialysis combined with HPLC/EC analysis it was shown that presentation to a rat of an inedible object (a piece of rubber) or an aversive object (food of bitter taste) instead of expected food caused a marked increase in extracellular glutamate level in n. accumbens. In rats not expecting food reinforcement, extracellular glutamate remained unchanged during presentation of these objects. Our findings suggest that dissociation between the expected biological value of a presented object and its real significance may be an important determinant for glutamate release control in n. accumbens during food behavior.     

Intralimbic evoked potentials in the formation of an instrumental food conditioned reflex to hippocampal electrostimulation in dogs]

In dogs with the electrodes implanted in the hippocampus, amygdala, septum and hypothalamus an instrumental alimentary conditioned reflex (CR) was elaborated to electrostimulation of the hippocampus. Intralimbic evoked potentials (EPs) were studied during the elaboration and extinction of this reflex and during stimulations of limbic structures conducted with the purpose of CR generalization checking. Late EP components in the lateral hypothalamus and central nucleus of the amygdala changed during CR elaboration and extinction and in the hippocampus during amygdala testing. In both cases the amplitude of trace positivity and of slow negative wave was less, when during stimulation of the structure an instrumental movement was initiated than at its absence.     

Glutamate release in the nucleus accumbens during competitive presentation of aversive and appetitive stimuli

By means of in vivo microdialysis combined with HPLC analysis, we have shown that extracellular glutamate level in the rat n. accumbens increases during a simultaneous presentation of a palatable diet and a tone previously paired with a footshock, the magnitude of the extracellular glutamate increase being proportional to the latency of food taking. In contrast, extracellular glutamate level remains unchanged when the diet is presented after the conditioned aversive stimulus or when the tone is given alone. These data suggest that the glutamate release evoked by the competitive presentation of the diet and the conditioned aversive stimulus appears to be related to the inhibition of a planned feeding response, whereas the choice between behavioural strategies may not contribute to this phenomenon.     

Adenosine receptor-mediated modulation of dopamine release in the nucleus accumbens depends on glutamate neurotransmission and N-methyl-D-aspartate receptor stimulation

Adenosine, by acting on adenosine A(1) and A(2A) receptors, exerts opposite modulatory roles on striatal extracellular levels of glutamate and dopamine, with activation of A(1) inhibiting and activation of A(2A) receptors stimulating glutamate and dopamine release. Adenosine-mediated modulation of striatal dopaminergic neurotransmission could be secondary to changes in glutamate neurotransmission, in view of evidence for a preferential colocalization of A(1) and A(2A) receptors in glutamatergic nerve terminals. By using in vivo microdialysis techniques, local perfusion of NMDA (3, 10 microm), the selective A(2A) receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680; 3, 10 microm), the selective A(1) receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT; 300, 1000 microm), or the non-selective A(1)-A(2A) receptor antagonist in vitro caffeine (300, 1000 microm) elicited significant increases in extracellular levels of dopamine in the shell of the nucleus accumbens (NAc). Significant glutamate release was also observed with local perfusion of CGS 21680, CPT and caffeine, but not NMDA. Co-perfusion with the competitive NMDA receptor antagonist dl-2-amino-5-phosphonovaleric acid (APV; 100 microm) counteracted dopamine release induced by NMDA, CGS 21680, CPT and caffeine. Co-perfusion with the selective A(2A) receptor antagonist MSX-3 (1 microm) counteracted dopamine and glutamate release induced by CGS 21680, CPT and caffeine and did not modify dopamine release induced by NMDA. These results indicate that modulation of dopamine release in the shell of the NAc by A(1) and A(2A) receptors is mostly secondary to their opposite modulatory role on glutamatergic neurotransmission and depends on stimulation of NMDA receptors. Furthermore, these results underscore the role of A(1) vs. A(2A) receptor antagonism in the central effects of caffeine.     

Regulation of 3H-dopamine release by presynaptic GABA and glutamate heteroreceptors in the synaptosomes of the rat nucleus accumbens

The influence of GABA, muscimol, delta-aminolevulinic acid (DALA), baclofen and L-glutamate on K+-evoked release of 3H-dopamine (3H-DA) from the rat brain n. accumbens crude synaptosomal fraction was studied in superfusion experimental conditions. Both GABA-receptor agonists--GABA and muscimol (50 microM) depressed the 3H-DA release by bicuculline- and picrotoxin-sensitive manner. On the contrary, glutamate, DALA and baclofen led to the increase in 3H-DA efflux independently of the presence of GABA-receptor antagonists. While the action of glutamate was antagonized by glutamate-receptor blocker--glutamic acid diethyl ester (GDEE), the effects of DALA and baclofen were suppressed upon adding to superfusion medium of GABA uptake inhibitors (nipecotic acid and 2,4-diaminobutyric acid) but not GDEE. The data obtained demonstrate that 3-H-DA secretion from n. accumbens is inhibited by GABA- and stimulated by glutamate-heteroreceptors. At the same time the mechanism of interaction between baclofen, DALA and GABA-uptake blockers effects with 3H-DA release needs special investigations.