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N‐Acetylcysteine differentially modulates cocaine‐ and amphetamine‐induced changes in extracellular dopamine in squirrel monkeys
Author(s) -
Bauzo Rayna M,
Morales Jose,
Kimmel Heather L.,
Howell Leonard L.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a684-d
Subject(s) - amphetamine , nucleus accumbens , pharmacology , microdialysis , dopamine transporter , dopamine , chemistry , dopaminergic , neuroscience , medicine , biology
Cocaine (COC) and amphetamine (AMPH) are psychostimulants that exert their behavioral effects by modifying dopamine transporter (DAT) function. These psychostimulants differ in their mechanisms of action ‐‐ COC blocks the DAT subsequently preventing the reuptake of extracellular dopamine (DA), whereas AMPH releases DA via reverse transport. Extracellular glutamate (GLU) regulates DA function in the mesolimbic pathway, which is involved in reinforcement. GLU levels modulate a number of behavioral parameters relevant to animal models of drug abuse. A number of rodent studies suggest that an acute COC injection increases both DA and GLU in the nucleus accumbens. This study focused on the cystine‐glumate transporter and its capacity to modify GLU tone in nonhuman primates challenged with COC or AMPH. N‐acetyl‐L‐cystine (NAC) is a cystine prodrug which increases GLU via the transporter. We hypothesized that systemic administration of NAC would increase GLU levels, subsequently attenuating COC‐ and AMPH‐induced changes of DA. In vivo microdialysis was performed on three adult male squirrel monkeys in order to monitor COC and AMPH‐induced changes of DA in the caudate. We found that systemic administration of NAC attenuated COC‐induced increases in DA but enhanced AMPH‐induced increases in DA. This difference may be due to the distinct mechanisms by which these drugs exert their effects on DAT. Further investigation of the mechanism by which NAC may be modifying COC and AMPH neurochemistry are warranted. Supported by USPHS Grants DA12514, DA000517, DA015092, and RR00165 and by NSF Agreement No. IBN‐9876754.