AMPT-induced monoamine depletion in humans: evaluation of two alternative [123I]IBZM SPECT procedures

Abstract

Purpose Acute monoamine depletion paradigms using alpha-methyl-para-tyrosine (AMPT) combined with single photon emission computed tomography (SPECT) have been used successfully to evaluate disturbances in central dopaminergic neurotransmission. However, severe side effects due to relatively high doses (4,500 to 8,000 mg) of AMPT have been reasons for study withdrawal. Thus, we assessed the effectiveness and tolerability of two alternative procedures, using lower doses of AMPT. Methods Six healthy subjects underwent three measurements of striatal dopamine D 2 receptor (D 2 R)-binding potential (BP ND ) with SPECT and the selective radiolabeled D 2 R antagonist [ 123 I]IBZM. All subjects were scanned in the absence of pharmacological intervention (baseline) and after two different depletion procedures. In the first depletion session, over 6 h, subjects were administered 1,500 mg of AMPT before scanning. In the second depletion session, over 25 h, subjects were administered 40 mg AMPT/kg body weight. We also administered the Subjective Well-being Under Neuroleptic Treatment Scale, a self-report instrument designed to measure the subjective experience of patients on neuroleptic medication. Results We found no change of mean D 2 R BP ND after the first and short AMPT challenge compared to the baseline. However, we found a significant increase in striatal D 2 R BP ND binding after the AMPT challenge adjusted for bodyweight compared to both other regimen. Although subjective well-being worsened after the prolonged AMPT challenge, no severe side effects were reported. Conclusions Our results imply a low-dosage, suitable alternative to the common AMPT procedure. The probability of side effects and study withdrawal can be reduced by this procedure.

SERT-to-DAT ratios in early Parkinson’s disease do not correlate with the development of dyskinesias

“…DAT binding in PD is commonly asymmetric, and the loss of binding is generally more profound in the putamen than in the caudate nucleus, which is also the case in this study, thus confirming the findings of earlier DAT SPECT studies in PD [20,23]. We hypothesized that if dopamine would be taken up predominantly by serotonergic neurons, then this phenomenon would first occur in the most affected striatal area.…”

“…Image acquisition was performed 24 h after injection. Images were corrected for attenuation and reconstructed in 3D [22,23]. …”

Dopamine depletion attenuates some behavioral abnormalities in a hyperdopaminergic mouse model of bipolar disorder

“…Additionally, it is important to note that AMPT can produce serious dose-related side effects, including crystalluria and acute dystonia (Abi-Dargham et al, 2000; Voruganti et al, 2001). Future studies should therefore also investigate low-dosage regimens, which have been demonstrated to be a suitable alternative that is free from severe side effects (Boot et al, 2008). Thus, it is possible to conduct cross-species relevant studies in animals and humans with previous studies supporting our findings that AMPT can reduce mania-like behavior.…”

Dopaminergic System Dysfunction in Recreational Dexamphetamine Users

“…Nondisplaceable binding potential (BP ND ) was calculated as follows: (mean striatal binding-mean binding occipital cortex)/mean binding occipital cortex. Standard templates with fixed ROIs were positioned on the striatum and occipital cortex (reflecting non-specific binding), as earlier described (Booij et al, 1997;Boot et al, 2008). dAMPHinduced decrease in […”

“…SPECT images were corrected for attenuation and reconstructed using iterative algorithms, as earlier described (Booij et al, 1997;Boot et al, 2008). Nondisplaceable binding potential (BP ND ) was calculated as follows: (mean striatal binding-mean binding occipital cortex)/mean binding occipital cortex.…”