GABAergic attenuation of cocaine-induced dopamine release and locomotor activity.
GABA modulates dopamine concentrations in the nucleus accumbens and corpus striatum. Using in vivo microdialysis techniques we examined this modulatory role and the extent to which three different GABAergic drugs can attenuate cocaine's ability to increase extracellular dopamine concentrations and gross locomotor activity. Ethanol, lorazepam (Ativan), and gamma-vinyl GABA (GVG) significantly and dose-dependently attenuated cocaine-induced dopamine release in the corpus striatum of freely moving animals. Unlike ethanol or lorazepam, however, GVG is not a sedative hypnotic in the doses used, and hence the strategy of selectively increasing GABAergic activity by suicide inhibition of the catabolic enzyme, GABA-transaminase, offers the unique advantage of attenuating cocaine-induced dopamine release without the apparent side effects typically associated with sedative hypnotics.
Dewey
S L
SL
Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973, USA.
Chaurasia
C S
CS
Chen
C E
CE
Volkow
N D
ND
Clarkson
F A
FA
Porter
S P
SP
Straughter-Moore
R M
RM
Alexoff
D L
DL
Tedeschi
D
D
Russo
N B
NB
Fowler
J S
JS
Brodie
J D
JD
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors; D000818:Animals; D003042:Cocaine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology*; D008140:Lorazepam / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018757:GABA Modulators; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin; D003042:Cocaine; D008140:Lorazepam; D004298:Dopamine