title: Differential responses to anticipation of reward after an acute dose of the designer drugs benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) alone and in combination using functional magnetic resonance imaging (fMRI).
abstract: BACKGROUND
  Functional magnetic resonance imaging (fMRI) studies have reported increased activation of the mesolimbic system in response to anticipation of rewarding stimuli. The anticipation of uncertain outcomes evokes activation in the amygdala, orbitofrontal cortex, inferior frontal gyrus and insula. Drugs known to effect dopaminergic and serotonergic neurons also alter regional activation.
  
  
  OBJECTIVE
  Benzylpiperazine (BZP) and/or trifluoromethylphenylpiperazine (TFMPP) have been recreationally used worldwide for more than a decade. BZP affects mainly dopaminergic neurons, while TFMPP has serotonergic effects.
  
  
  METHODS
  We investigated the effects of an acute dose of BZP, TFMPP or a combination of BZP and TFMPP on the anticipation of reward in a double-blind, placebo-controlled, crossover study using fMRI. An event-related gambling paradigm was completed by healthy controls 90 min after taking an oral dose of either BZP (200 mg), TFMPP (either 50 or 60 mg), BZP + TFMPP (100 + 30 mg) or placebo.
  
  
  RESULTS
  After giving BZP, the anticipation of a $4 reward decreased the activation of the inferior frontal gyrus, insula and occipital regions in comparison to placebo. TFMPP increased the activation of the putamen but decreased the activity in the insula relative to placebo. When BZP and TFMPP were given in combination, activation of the rolandic operculum occurred. The magnitude of reward also affected neural correlates.
  
  
  CONCLUSIONS
  We propose that the effects of BZP and TFMPP on dopaminergic and serotonergic circuitry, respectively, reflect regional changes. The dopaminergic effects of BZP appear to increase positive arousal and subsequently reduce the response to uncertainty, while TFMPP appears to alter the response to uncertainty by increasing emotional responses.
authors.affiliation: School of Pharmacy and Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand, l.curley@auckland.ac.nz.
authors.forename: Louise E
authors.initials: LE
authors.lastname: Curley
authors.forename: Robert R
authors.initials: RR
authors.lastname: Kydd
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Kirk
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Russell
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D018592:Cross-Over Studies; D015198:Designer Drugs / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005715:Gambling / Q000523:psychology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D012201:Reward; D012701:Serotonin / Q000378:metabolism; D055815:Young Adult
chemical_list: D015198:Designer Drugs; D010879:Piperazines; C018406:1-(3-trifluoromethylphenyl)piperazine; D012701:Serotonin; C006737:1-benzylpiperazine; D004298:Dopamine