In vivo evidence that genetic background controls impulse-dependent dopamine release induced by amphetamine in the nucleus accumbens.
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.
Ventura
Rossella
R
Dipartimento di Psicologia, University La Sapienza, Rome, Italy.
Alcaro
Antonio
A
Mandolesi
Laura
L
Puglisi-Allegra
Stefano
S
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D017551:Microdialysis; D009498:Neurotoxins / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013045:Species Specificity; D009435:Synaptic Transmission / Q000502:physiology*
D015259:Dopamine Agents; D009498:Neurotoxins; D010879:Piperazines; D026941:Sodium Channel Blockers; C043425:vanoxerine; D000661:Amphetamine; D004298:Dopamine