Activation of the NO-ergic system of the nucleus accumbens on presentation of contextual danger signals.

Studies in Sprague-Dawley rats using intracerebral microdialysis combined with HPLC showed that presentation of the animals with a chamber in which they had previously acquired a conditioned reflex fear reaction (combination of a tone and electric shocks) led to increases in extracellular citrulline (a co-product of NO synthesis) in the medial segment of the nucleus accumbens. This increase was prevented by local administration of the NO synthase inhibitor 7-nitroindazole (0.5 mM). The increase was significantly smaller in amplitude than the increase in the citrulline level induced by combined presentation of the tone and the chamber but was no different from changes in citrulline levels seen during this test in the lateral segment of the nucleus accumbens. These data provide evidence that contextual danger signals activate neuronal NO synthase in the medial and perhaps the lateral segments of the nucleus accumbens, leading to increases in extracellular citrulline and, probably, increased NO production in this part of the brain.

[Sound signals of danger activate the nitrergic system of the medial nucleus accumbens].

It was shown in Sprague-Dawley rats by means of in vivo microdialysis combined with HPLC analysis that presentations to the animals in a home cage of a tone previously paired with a footshock in an experimental chamber produced an increase in extracellular levels of citrulline (an NO co-product) in the medial n. accumbens. The increase was prevented by intraaccumbal infusions of 7-nitroindasole (0.5 mM), a neuronal NO synthase inhibitor and was not observed in rats previously exposed to unpaired tone and footshock presentations and in controls with microdialysis probes implanted into the lateral n. accumbens. The results indicate that sound signals of danger produce a neuronal NO synthase activation within the medial n. accumbens, which leads to citrulline formation and, very likely, to NO production in this brain area.

Effects of blockade of dopamine D2 receptors on extracellular citrulline levels in the nucleus accumbens during performance of a conditioned reflex fear response.

Vital microdialysis studies on Sprague-Dawley rats using HPLC showed that performance of a conditioned reflex fear response was accompanied by an increase in the extracellular level of citrulline (a coproduct of nitric oxide synthesis) in the nucleus accumbens. Administration of the dopamine D(2) receptor antagonist raclopride (10 microM) into the nucleus accumbens decreased the magnitude of the increase in the extracellular citrulline level in this structure during performance of the conditioned reflex fear response but had no effect on its behavioral measures (the level of freezing). Doses increased investigative activity in a novel context which had been inhibited by acquisition of the conditioned reflex fear response, without affecting the investigative behavior of control animals. These data suggest that the dopaminergic input and dopamine D(2) receptors control the activity of the NO-ergic system of the nucleus accumbens during performance of the conditioned reflex fear response and may control "transfer" of fear to another behavioral situation.

[NO-ergic system activation in the nucleus accumbens during presentation of contextual signals of danger].

In Spregue-Dawley rats by means of in vivo microdialysis combined with HPLC analysis, presentation of a chamber in which a conditioned fear response was previously acquired (tone(+) +footshock), resulted in an increase in extracellular level of citrulline (an NO co-product) in the medial nucleus accumbens. This increase was prevented by intraaccumbal infusion of 7-nitraindazole (0.5 mM), an NO synthase inhibitor. It was less than a rise in citrulline extracellular level induced by a combined presentation the chamber and the tone, but did not differ from citrulline changes occurring during the chamber presentation in the lateral nucleus accumbens. The data obtained indicate that conditioned signals of danger cause neuronal NO synthase activation in the medial and, probably, in the lateral nucleus accumbens which produces the rise in extracellular citrulline level and, likely, in NO formation in this brain area.

Dopamine D1 receptors regulate the extracellular citrulline level in the nucleus accumbens during performance of a conditioned reflex fear reaction.

Intracerebral microdialysis studies on Sprague-Dawley rats using HPLC showed that performance of a conditioned reflex fear reaction was accompanied by an increase in the extracellular citrulline (a co-product of nitric oxide synthesis) level in the nucleus accumbens. Administration of the selective D1 receptor antagonist SCH-23390 (100 microM) into the nucleus accumbens had no long-lasting effect on the extracellular citrulline level in this structure, but reduced the magnitude of the increase in the citrulline level seen on performance of the conditioned reflex fear reaction. These data suggest that the dopaminergic input of the nucleus accumbens acts via D1 receptors to increase NO synthase activity and nitric oxide production during performance of the conditioned reflex fear reaction.

[Effect of D2 dopamine receptor blockade on extracellular citrulline levels in the nucleus accumbens during expression of conditioned fear response].

By means of in vivo microdialysis combined with HPLC analysis it was shown that levels of extracellular citrulline (NO co-product) in the rat n. accumbens increased during expression of a conditioned fear response. Intraaccumbal infusions of a D2 receptor antagonist raclopride (10 microM) decreased the rise of extracellular citrulline produced by expression of the response but did not change behavioral characteristics of conditioned freezing. The raclopride infusions increased exploratory activity inhibited by acquisition of conditioned fear but did not affect the exploration of control rats. These data suggest that dopaminergic input to the n. accumbens and D2 dopamine receptors regulate activity of the accumbal nitrergic system during conditioned fear response and possibly control fear transfer to another behavioral situation.

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.

[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.