title: Prefrontal GABA levels in cocaine-dependent subjects increase with pramipexole and venlafaxine treatment.
abstract: 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.
authors.affiliation: Division of Psychiatry, Boston University School of Medicine, and Boston VA Healthcare System, Boston, MA, USA. streeter@bu.edu
authors.forename: Chris C
authors.initials: CC
authors.lastname: Streeter
authors.forename: John
authors.initials: J
authors.lastname: Hennen
authors.forename: Yong
authors.initials: Y
authors.lastname: Ke
authors.forename: J Eric
authors.initials: JE
authors.lastname: Jensen
authors.forename: Ofra
authors.initials: O
authors.lastname: Sarid-Segal
authors.forename: Leanne E
authors.initials: LE
authors.lastname: Nassar
authors.forename: Clifford
authors.initials: C
authors.lastname: Knapp
authors.forename: Angela A
authors.initials: AA
authors.lastname: Meyer
authors.forename: Tae
authors.initials: T
authors.lastname: Kwak
authors.forename: Perry F
authors.initials: PF
authors.lastname: Renshaw
authors.forename: Domenic A
authors.initials: DA
authors.lastname: Ciraulo
mesh_terms: 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*
chemical_list: 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