Amphetamine is known to increase dopamine (DA) release by acting directly on dopamine transporters (DAT), primarily through a mechanism that is independent of impulse flow. We present evidence to show that impulse-dependent increase in DA outflow in the nucleus accumbens (NAc) is produced by amphetamine depending on genetic background. Systemic amphetamine produced higher accumbal DA release in the widely exploited C57BL/6J background than in the DBA/2J. By contrast, intra-accumbens perfusion using increasing doses of amphetamine dramatically increased DA outflow in the DBA/2J background, whereas very low DA outflow was evident in C57BL/6J mice. The fast sodium channel blocker tetrodotoxin infused through the microdialysis probe abolished accumbal DA release induced by systemic amphetamine only in the C57BL/6J background. Finally, medial prefrontal excitotoxic lesion abolished amphetamine-induced mesoaccumbens DA release in C57BL/6J mice, without significantly affecting it in the DBA/2J background. These results represent the first functional evidence in an in vivo study that amphetamine can increase DA release in the NAc mainly through an impulse-dependent mechanism regulated by prefronto-cortical glutamatergic transmission. Moreover, they point to a genetic control of impulse-dependent DA release in the accumbens, providing an exploitable tool to investigate aetiological factors involved in psychopathology and drug addiction.

In vivo evidence that genetic background controls impulse-dependent dopamine release induced by amphetamine in the nucleus accumbens / Ventura, Rossella; Antonio, Alcaro; Laura, Mandolesi; PUGLISI ALLEGRA, Stefano. - In: JOURNAL OF NEUROCHEMISTRY. - ISSN 0022-3042. - 89:2(2004), pp. 494-502. [10.1111/j.1471-4159.2004.02342.x]

In vivo evidence that genetic background controls impulse-dependent dopamine release induced by amphetamine in the nucleus accumbens

VENTURA, Rossella;PUGLISI ALLEGRA, Stefano
2004

Abstract

Amphetamine is known to increase dopamine (DA) release by acting directly on dopamine transporters (DAT), primarily through a mechanism that is independent of impulse flow. We present evidence to show that impulse-dependent increase in DA outflow in the nucleus accumbens (NAc) is produced by amphetamine depending on genetic background. Systemic amphetamine produced higher accumbal DA release in the widely exploited C57BL/6J background than in the DBA/2J. By contrast, intra-accumbens perfusion using increasing doses of amphetamine dramatically increased DA outflow in the DBA/2J background, whereas very low DA outflow was evident in C57BL/6J mice. The fast sodium channel blocker tetrodotoxin infused through the microdialysis probe abolished accumbal DA release induced by systemic amphetamine only in the C57BL/6J background. Finally, medial prefrontal excitotoxic lesion abolished amphetamine-induced mesoaccumbens DA release in C57BL/6J mice, without significantly affecting it in the DBA/2J background. These results represent the first functional evidence in an in vivo study that amphetamine can increase DA release in the NAc mainly through an impulse-dependent mechanism regulated by prefronto-cortical glutamatergic transmission. Moreover, they point to a genetic control of impulse-dependent DA release in the accumbens, providing an exploitable tool to investigate aetiological factors involved in psychopathology and drug addiction.
2004
d-amphetamine; dopamine; genotype; glutamate; nucleus accumbens; prefrontal cortex
01 Pubblicazione su rivista::01a Articolo in rivista
In vivo evidence that genetic background controls impulse-dependent dopamine release induced by amphetamine in the nucleus accumbens / Ventura, Rossella; Antonio, Alcaro; Laura, Mandolesi; PUGLISI ALLEGRA, Stefano. - In: JOURNAL OF NEUROCHEMISTRY. - ISSN 0022-3042. - 89:2(2004), pp. 494-502. [10.1111/j.1471-4159.2004.02342.x]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/141
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