Control of within-binge cocaine-seeking by dopamine and glutamate in the core of nucleus accumbens.
BACKGROUND
Dopamine and glutamate are thought to interact in the ventral striatum and to play important roles there in the cocaine-seeking of cocaine-experienced animals.


OBJECTIVE
We sought to determine the relative roles of the two transmitters in the two major zones of the nucleus accumbens (NAS), the core and shell subregions.


METHODS
We assessed the effects of dopamine and glutamate receptor blockade in the core and shell on intravenous cocaine self-administration in rats. Trained animals were allowed to self-administer cocaine for an initial hour, and then D1-type or D2-type dopamine receptor blockers or NMDA-type or AMPA-type glutamate receptor blockers were infused by reverse microdialysis into one of the two regions for an additional 3 h of testing.


RESULTS
The D1-type antagonist SCH23390 and the D2-type antagonist raclopride each increased cocaine intake whereas the AMPA-type antagonist CNQX decreased responding when infused into the core. SCH23390 increased cocaine intake less strongly when infused into the shell, while raclopride and CNQX were each ineffective when infused into the shell. The NMDA-antagonist CPP failed to affect cocaine self-administration when infused into either site.


CONCLUSIONS
These findings implicate the core of NAS in the maintenance of established cocaine self-administration in trained animals, despite the fact that the reinforcement of responding in untrained animals appears to results from cocaine actions in the olfactory tubercle and medial shell and not the core of accumbens.
Behavioral Neuroscience Branch, Intramural Research Program, NIDA/NIH/DHHS, Baltimore, MD 21224, USA. nsuto@mprc.umaryland.edu.
Nobuyoshi
N
Suto
Laurel E
LE
Ecke
Roy A
RA
Wise
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D016739:Behavior, Addictive / Q000517:prevention & control*; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000503:physiopathology* / Q000523:psychology; D004298:Dopamine / Q000502:physiology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000502:physiology*; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000503:physiopathology; D009833:Olfactory Pathways / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D020318:Rats, Long-Evans; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012055:Reinforcement Schedule; D012646:Self Administration
D065127:Dopamine D2 Receptor Antagonists; D018091:Receptors, AMPA; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D003042:Cocaine; D004298:Dopamine