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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)

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Abstract

Rationale

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.

Objectives

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.

Conclusion

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.

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Acknowledgments

This work was supported by the Faculty Development Research Fund, School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland. The authors would like to thank Dr. Donald McLaren for his fMRI guidance in the data analysis stage of this research.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. School of Pharmacy and Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand

    Louise E. Curley & Bruce R. Russell

  2. Department of Psychological Medicine and Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand

    Robert R. Kydd

  3. Department of Psychology and Centre for Brain Research, Faculty of Science, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand

    Ian J. Kirk

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  1. Louise E. Curley
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Correspondence to Louise E. Curley.

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Curley, L.E., Kydd, R.R., Kirk, I.J. et al. 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). Psychopharmacology 229, 673–685 (2013). https://doi.org/10.1007/s00213-013-3128-3

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