Prefrontal GABA levels in cocaine-dependent subjects increase with pramipexole and venlafaxine treatment.
BACKGROUND
There is evidence that prefrontal lobe GABA levels are low in cocaine-dependent (CD) individuals, and treatment with GABA agonists decreases cocaine self-administration.


OBJECTIVE
The aim of the study is to measure changes in GABA levels in CD subjects at baseline and after 8 weeks of treatment with pramipexole, venlafaxine, or placebo.


METHODS
CD subjects enrolled in a treatment trial for cocaine dependence were recruited for this proton (1H) magnetic resonance spectroscopy (MRS) study. GABA levels in the prefrontal lobe were measured before and after treatment.


RESULTS
Mean percentage changes in GABA levels were as follows: pramipexole +17.0+/-28.0%, venlafaxine +13.0+/-11.0%, and placebo -2.1+/-19.5%. Pramipexole-treated subjects had significantly increased brain GABA levels compared to placebo (p=0.031). Venlafaxine treatment was nonsignificantly associated with increased GABA levels compared to placebo (p=0.16). The overall statistical model for the effect of drug treatment vs placebo on brain GABA levels, including adjustment for baseline levels, was highly significant (p=0.002). Despite significant changes in GABA levels, there were no significant differences in the number of urine samples positive for cocaine metabolites.


CONCLUSIONS
This study demonstrates that 1H MRS can measure changes in GABA levels following pharmacologic treatment. The increase in GABA levels, although significant, is modest compared to other MRS studies of depression or epilepsy associated with clinical improvements. The failure to see larger increases in GABA levels and an associated reduction in cocaine consumption may reflect the relatively low doses of medication used.
Streeter
Chris C
CC
Division of Psychiatry, Boston University School of Medicine, and Boston VA Healthcare System, Boston, MA, USA. streeter@bu.edu
Hennen
John
J
Ke
Yong
Y
Jensen
J Eric
JE
Sarid-Segal
Ofra
O
Nassar
Leanne E
LE
Knapp
Clifford
C
Meyer
Angela A
AA
Kwak
Tae
T
Renshaw
Perry F
PF
Ciraulo
Domenic A
DA
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use; D052160:Benzothiazoles; D019970:Cocaine-Related Disorders / Q000188:drug therapy*; D003511:Cyclohexanols / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000600:supply & distribution; D000077487:Pramipexole; D017397:Prefrontal Cortex / Q000187:drug effects*; D011522:Protons; D012189:Retrospective Studies; D013844:Thiazoles / Q000627:therapeutic use; D013997:Time Factors; D000069470:Venlafaxine Hydrochloride; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018687:Antidepressive Agents, Second-Generation; D000975:Antioxidants; D052160:Benzothiazoles; D003511:Cyclohexanols; D011522:Protons; D013844:Thiazoles; D005680:gamma-Aminobutyric Acid; D009538:Nicotine; D000069470:Venlafaxine Hydrochloride; D000077487:Pramipexole