Endogenous Opioid Release in the Human Brain Reward System Induced by Acute Amphetamine Administration

doi:10.1016/j.biopsych.2012.01.027

Biological Psychiatry

Volume 72, Issue 5, 1 September 2012, Pages 371-377

https://doi.org/10.1016/j.biopsych.2012.01.027 Get rights and content

Background

We aimed to demonstrate a pharmacologically stimulated endogenous opioid release in the living human brain by evaluating the effects of amphetamine administration on [¹¹C]carfentanil binding with positron emission tomography (PET).

Methods

Twelve healthy male volunteers underwent [¹¹C]carfentanil PET before and 3 hours after a single oral dose of d-amphetamine (either a “high” dose, .5 mg/kg, or a sub-pharmacological “ultra-low” dose, 1.25 mg total dose or approximately .017 mg/kg). Reductions in [¹¹C]carfentanil binding from baseline to post-amphetamine scans (ΔBP_ND) after the “high” and “ultra-low” amphetamine doses were assessed in 10 regions of interest.

Results

[¹¹C]carfentanil binding was reduced after the “high” but not the “ultra-low” amphetamine dose in the frontal cortex, putamen, caudate, thalamus, anterior cingulate, and insula.

Conclusions

Our findings indicate that oral amphetamine administration induces endogenous opioid release in different areas of human brain, including basal ganglia, frontal cortex areas, and thalamus. The combination of an amphetamine challenge and [¹¹C]carfentanil PET is a practical and robust method to probe the opioid system in the living human brain.

Section snippets

Study Design

This was a single-blind, nonrandomized, between-groups design study. Twelve healthy male volunteers (details in Supplementary Methods and Table S1 in Supplement 1) were examined with [¹¹C]carfentanil PET before and 3 hours after an oral administration of either a high (.5 mg/kg, n = 6) or an ultra-low dose (1.25 mg total dose or approximately .017 mg/kg; n = 6) of d-amphetamine. The ultra-low dose was included to control for any effects of expectation of receiving amphetamine and was not

Results

High baseline [¹¹C]carfentanil binding was observed in the ventral striatum, caudate, putamen, thalamus, and cingulate cortex. Other areas with baseline [¹¹C]carfentanil BP_ND > 1 were the hypothalamus, amygdala, insula, PAG, and medial orbital cortex (Figure S1 in Supplement 1).

Discussion

We have demonstrated a reduction in the binding of [¹¹C]carfentanil to the MOR in the human basal ganglia, thalamus, and frontal cortex after an administration of a pharmacologically relevant dose of d-amphetamine. Our results are consistent with preclinical evidence that amphetamine induces a significant increase in the extra-neuronal concentration of opioid peptides with high affinity for MOR (21, 22). The availability of the MOR to bind [¹¹C]carfentanil can be reduced by the release of a

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Archival ReportEndogenous Opioid Release in the Human Brain Reward System Induced by Acute Amphetamine Administration

Background

Methods

Results

Conclusions

Section snippets

Study Design

Results

Discussion

Drug Alcohol Depend

Trends Neurosci

Neuroscience

Neuroscience

Biol Psychiatry

Pain

Brain Res

Biol Psychiatry

Biol Psychiatry

Eur J Pharmacol

Neuroimage

Neuroimage

Neuroscience

Brain Res

Neurosci Lett

Jpn J Pharmacol

Curr Opin Pharmacol

Brain Res

Neuroscience

Brain Res

Neuroimage

Neuroscience

Blocking central opiate function modulates hedonic impact and anterior cingulate response to rewards and losses

J Neurosci

Regional mu opioid receptor regulation of sensory and affective dimensions of pain

Science

Pharmacological differentiation of opioid receptor antagonists by molecular and functional imaging of target occupancy and food reward-related brain activation in humans

Mol Psychiatry

Opioids and Anxiety

J Psychopharmacol

Regulation of human affective responses by anterior cingulate and limbic mu-opioid neurotransmission

Arch Gen Psychiatry

Archival Report
Endogenous Opioid Release in the Human Brain Reward System Induced by Acute Amphetamine Administration