Glutamatergic regulation of extracellular citrulline levels in the nucleus accumbens during an emotional conditioned reflex.

Intracerebral microdialysis and high-performance liquid chromatography were used to demonstrate that the acquisition and execution of an emotional conditioned reflex in Sprague-Dawley rats are accompanied by increases in extracellular citrulline (a co-product of nitric oxide synthesis) levels in the nucleus accumbens. Injection of the selective NMDA glutamate receptor antagonist MK-801 (100 microM) into the nucleus accumbens significantly decreased the increase in extracellular citrulline seen in this structure on acquisition of the emotional conditioned reflex and completely blocked the increase induced by execution of the reflex. These data suggest that during the acquisition and execution of an emotional conditioned reflex, the glutamatergic input of the nucleus accumbens acts on NMDA receptors to stimulate nitric oxide production in this part of the brain.

NO synthase-dependent increases in extracellular citrulline levels in the nucleus accumbens in an emotional conditioned reflex.

Intracerebral microdialysis/HPLC studies in Sprague-Dawley rats showed that the acquisition and execution of an emotional conditioned reflex was accompanied by an increase in the extracellular citrulline level in the nucleus accumbens; citrulline is a co-product of nitric oxide synthesis. The increase in the citrulline level evoked by execution of this reflex decreased after injection of 7-nitroindazole (0.5 mM), a selective inhibitor of neuronal NO synthase, into the nucleus accumbens, and was completely blocked by injection of N-nitroarginine (0.5 mM), a non-selective inhibitor NO synthase. The increase in the nucleus accumbens citrulline level seen during execution of the emotional conditioned reflex was prevented by administration of both of these NO synthase inhibitors. These data suggest that during the acquisition and execution of the emotional conditioned reflex, there is an increase in nitric oxide production in the nucleus accumbens, which arises predominantly as a result of activation of neuronal NO synthase.

[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.

Extracellular citrulline levels in the nucleus accumbens during the acquisition and extinction of a classical conditioned reflex with pain reinforcement.

Studies on Sprague-Dawley rats using in vivo microdialysis and HPLC showed that the acquisition and performance of a classical conditioned reflex with pain reinforcement was accompanied by increases in the concentrations of citrulline (a side product of nitric oxide formation) and arginine (the substrate of NO synthase) in the intercellular space of the nucleus accumbens. During extinction of the reflex, there was a decrease in the elevation of extracellular citrulline in this brain structure, which correlated with the extent of extinction of the reflex. Recovery of the reflex led to increases in arginine and citrulline levels in the nucleus accumbens. These data suggest that there is an increase in nitric oxide production in the nucleus accumbens during the acquisition and performance of a classical conditioned reflex with pain reinforcement, which decreases as the reflex is extinguished and recovers with recovery of the reflex.

Effects of local infusions of apomorphine on the extracellular citrulline level in the striatum: Involvement of D1 and D2 dopamine receptors.

Studies using vital microdialysis and high-performance liquid chromatography showed that local infusion of the NO synthase inhibitor N-nitro-L-arginine (1 mM) into the striatum decreased, while infusion of the dopamine receptor agonist apomorphine (100 microM) increased the level of citrulline (a side product of nitric oxide synthesis) in the intercellular space of this structure in Sprague-Dawley rats. The increase in the citrulline level induced by infusions of apomorphine was completely prevented by local infusions of N-nitro-L-arginine (1 mM) and raclopride (10 microm), a dopamine D2 receptor blocker, but not by infusion of SCH-23390 (50 microm), a dopamine D1 receptor blocker. These data suggest that the increase in extracellular citrulline in the striatum induced by dopaminergic stimulation results from local increases in NO synthase activity and that this effect involves D2, but not D1 dopamine receptors.

[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.

[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.

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

In vivo intracerebral microdialysis/HPLC studies on Sprague-Dawley rats showed that simultaneous presentation of food and a tone previously combined with a pain stimulus was accompanied by transient elevation of the glutamate level in the extracellular space of the nucleus accumbens, the extent of this increase being proportional to the latent period of initiation of the act of eating. Conversely, sequential presentation of the conditioned aversive signal followed by food and isolated presentation of the conditioned aversive signal alone were not accompanied by changes in the level of extracellular glutamate. It is suggested that glutamate release in the nucleus accumbens in conditions of competition between presentation of food and a tone previously combined with pain stimulation is not related to the process of selecting between the aversive and appetitive strategies of behavior, but may be associated with inhibition of preparation to perform or performance of the food-related behavior.

[Influence of local administration of apomorphine on citrulline extracellular level in the striatum: participation of the dopamine D1 and D2 receptors].

By means of in vivo microdialysis combined with HPLC analysis, we have shown that local infusions of 1 mM N-nitro-L-arginine (NO-synthase inhibitors) in the rat striatum reduced, and infusions of 100 microM apomorphine (agonists of the dopamine receptors) increased the level of citrulline (a NO co-product) in extracellular space of this structure. The apomorphine-induced increase in citrulline extracellular levels in the striatum was completely prevented by infusions of N-nitro-L-arginine in this structure, and 10 microM raclopride (dopamine D2 receptor blocker), but not by infusions of 50 microM SCH-23390 (dopamine D1 receptor blocker). The data obtained suggest that the increase in citrulline extracellular levels in striatum resulted from local activation of NO-synthase, and this effect is mediated by D2 rather than D1 dopamine receptors.

[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.