ORIGINAL ARTICLE

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

Erik Boot & Jan Booij & Gregor Hasler &Janneke R. Zinkstok & Lieuwe de Haan &Don H. Linszen & Thrse A. van Amelsvoort

Received: 21 September 2007 /Accepted: 15 January 2008 / Published online: 19 February 2008# The Author(s) 2008

AbstractPurpose Acute monoamine depletion paradigms usingalpha-methyl-para-tyrosine (AMPT) combined with singlephoton emission computed tomography (SPECT) havebeen used successfully to evaluate disturbances in centraldopaminergic neurotransmission. However, severe sideeffects due to relatively high doses (4,500 to 8,000 mg) ofAMPT have been reasons for study withdrawal. Thus, weassessed the effectiveness and tolerability of two alternativeprocedures, using lower doses of AMPT.Methods Six healthy subjects underwent three measure-ments of striatal dopamine D2 receptor (D2R)-bindingpotential (BPND) with SPECT and the selective radiolabeledD2R antagonist [

123I]IBZM. All subjects were scanned inthe absence of pharmacological intervention (baseline) andafter two different depletion procedures. In the firstdepletion session, over 6 h, subjects were administered1,500 mg of AMPT before scanning. In the second

depletion session, over 25 h, subjects were administered40 mg AMPT/kg body weight. We also administered theSubjective Well-being Under Neuroleptic Treatment Scale,a self-report instrument designed to measure the subjectiveexperience of patients on neuroleptic medication.Results We found no change of mean D2R BPND after thefirst and short AMPT challenge compared to the baseline.However, we found a significant increase in striatal D2RBPND binding after the AMPT challenge adjusted forbodyweight compared to both other regimen. Althoughsubjective well-being worsened after the prolonged AMPTchallenge, no severe side effects were reported.Conclusions Our results imply a low-dosage, suitablealternative to the common AMPT procedure. The probabilityof side effects and study withdrawal can be reduced by thisprocedure.

Keywords AMPT. Dopamine . [123I]IBZM . SPECT. SWN

Introduction

Several neuropsychiatric disorders have been associatedwith disturbances of the catecholaminergic neurotransmit-ters dopamine (DA) and norepinephrine (NE), includingschizophrenia [1], mood disorders [2, 3] and Parkinsonsdisease [4]. Strategies to increase our knowledge of theseneurotransmitter systems combining pharmacologic chal-lenges with neuroimaging techniques like positron emissiontomography (PET) and single photon emission computedtomography (SPECT) are extensively used. The develop-ment of such experimental procedures has allowed for theinvestigation of associations between the function ofneurotransmitters and neuropsychiatric disorders. For ex-ample, employing such a challenge paradigm, it has been

Eur J Nucl Med Mol Imaging (2008) 35:13501356DOI 10.1007/s00259-008-0739-8

E. Boot (*) : J. R. Zinkstok : L. de Haan :D. H. Linszen :T. A. van AmelsvoortDepartment of Psychiatry, Academic Medical Centre (AMC),University of Amsterdam,Meibergdreef 5,1070 AWAmsterdam, The Netherlandse-mail: h.j.boot@amc.uva.nl

J. BooijDepartment of Nuclear Medicine, AMC,Amsterdam, The Netherlands

G. HaslerDepartment of Psychiatry, University Hospital,Zrich, Switzerland

E. BootDe Bruggen, Centre for People with Intellectual Disability,Zwammerdam, The Netherlands

shown that there is an increased occupancy of DA D2receptors (D2R) by endogenous DA in schizophrenicpatients compared to the controls [5]. In addition, mono-amine depletion studies demonstrate that, although mono-amine systems are probably important in the vulnerabilityto mood lability, there is no simple direct causal relationbetween catecholamines and mood, as proposed in themonoamine hypothesis of mood disorders [3, 6, 7].

Catecholamine depletion paradigms have been used mostfrequently in two ways. First, dietary restriction of thecatecholamine precursors phenylalanine and tyrosine hasbeen used in the so-called acute tyrosine depletion orphenylalanine/tyrosine depletion (APTD) [6]. APTD involvesthe restriction of the precursor amino acid, phenylalanine andtyrosine, intake during 1 day, followed by the consumptionof an amino acid mixture that lacks phenylalanine andtyrosine the next morning [6]. As this mixture stimulatesprotein synthesis, which requires phenylalanine and tyrosine,less of the amino acids phenylalanine and tyrosine areavailable for the brain [6]. Although the biochemical effectsof this procedure in the brain remain unclear, it is believedthat APTD mainly affects DA synthesis [6]. Experience withAPTD challenges in combination with neuroimaging techni-ques is limited, and we are aware of only two such studies.In one PET study in seven healthy men, APTD induced anincreased [11C]raclopride binding by a mean of 6% [8].Second, Leyton et al. [9] presented a PET study in eighthealthy men that provided evidence for APTD to decreaseamphetamine-induced DA release. Except for limited expe-riences, disadvantages of APTD include an unpalatable taste[10] and nausea [11], and study subjects tend to report thatthey feel less good after this diet [12]. Another way to inducecatecholamine depletion is by administration of alpha-methyl-para-tyrosine (AMPT). AMPT is a competitiveinhibitor of the rate-limiting enzyme of catecholaminesynthesis and tyrosine hydroxylase [13], and affects bothDA and NE synthesis [6]. It has been suggested that AMPTproduces a substantially greater impairment in DA releasethan tyrosine depletion does [11]. However, side effects,which are dose-related, may be serious and can be reason forwithdrawal. For example, severe side effects that have beenreported previously include serious psychiatric symptoms[14], crystalluria and acute dystonia [5, 15]. Common AMPTdepletion procedures involve a 25- to 48-h study period inwhich study subjects administer a total amount of 4,5008,000 mg AMPT [6]. Nevertheless, other studies showedsignificant depletion effects on indirect dopaminergicmarkers including measures of peripheral DA, its metabolitesand the hormone prolactin (PRL) after lower doses of AMPT[16, 17]. For this, it could be hypothesized that, to inducemeasurable effects of DA depletion with PET or SPECT,lower dosages than the common 4,5008,000 mg AMPTmay be sufficient.

Moreover, lower doses of AMPT could possibly reduceside effects as well and would therefore allow testingsubjects in complex neuropsychological tasks and imagingexperiments. To estimate the effects of reduced dopaminer-gic neurotransmission, we administered a self-report instru-ment, the Subjective Well-being Under NeurolepticTreatment Scale (SWN) [1820]. For example, initialstudies using this instrument provided evidence thatnegative subjective experience is related to high DA D2Roccupancy in patients treated with antipsychotic medica-tion, reflecting a hypodopaminergic state [21, 22].

The aim of this study was to assess the effectiveness andtolerability of two alternative procedures for the commonly usedacute AMPT depletion challenge paradigm and simultaneousD2R SPECT imaging, using relatively low doses of AMPT.

Materials and methods

Subjects

The study protocol was approved by the Ethics Committeeof the Academic Medical Centre of Amsterdam. Eachparticipant gave written informed consent after explainingthe full study procedure. Six healthy volunteers older than18 years but younger than 40 years were included. Theexclusion criteria were (1) current or past psychiatrichistory, (2) current or previous exposure to antipsychoticor stimulant medication, (3) lifetime history of alcohol orsubstance abuse or dependence, (4) concomitant or pastsevere medical conditions and (5) pregnancy, based on aclinical interview and the urine HCG test.

Depletion regimen

Each subject was scanned three times, once in the baselinestate (D1) and twice after DA depletion (D2, D3) with aninterval ranging from one to nine and from 49 to 110 weeks,respectively. DA depletion was induced by oral adminis-tration of AMPT. In a short AMPT challenge session usinga low fixed dose of AMPT (D2), the total AMPT doseadministered was 1,500 mg over 4 h. The first dose(500 mg) was given on the morning (D2T0). Subsequently,500 mg AMPT was administered 2 h after baseline (D2T2)and 4 h after baseline (500 mg, D2T4). Scans were acquired1 h after the last AMPT dose (D2T5).

In the second and more prolonged challenge session(D3), DA depletion was induced by oral administration ofAMPT over 24 h. The exact AMPT dose was calculated ona per weight basis (40 mg/ kg body weight). The overallAMPT dose was spread equally in 250-mg capsules overfour time points. Three doses were given 1 day before thescan: at baseline (D3T0), 6 h after baseline (D3T6) and 12 h

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after baseline (D3T12). The last AMPT dose was given 24 hafter D3T0 (D3T24) and 1 h before the beginning of thescanning session (D3T25). To prevent the formation ofAMPT crystals in the urine, subjects were instructed todrink plenty of fluids.

SPECT protocol

All subjects took potassium iodide orally (three doses of40 mg on the day before imaging and 80 mg just beforeimaging) to block thyroid uptake of free radioactive iodide.The subjects underwent three measurements of D2R-bindingpotential (BPND) [23], with SPECT and the selective iodine-123-labeled D2R antagonist (S)-()-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide([123I]IBZM), using the sustained equilibrium/constant infu-sion technique [24]. A total [123I]IBZM dose (specificactivity>200 MBq/nmol and radiochemical purity>95%) ofapproximately 56 MBq was given as a bolus, followed by acontinuous infusion for the duration of the experiment(180 min). The bolus to hourly infusion ratio was approx-imately 4.0 [25]. This protocol of administration induces astate of sustained binding equilibrium after 120 min [25].SPECT data were acquired for approximately 60 min, from120 to 180 min after the initiation of [123I]IBZM adminis-tration. SPECT studies were performed using a 12-detectorsingle slice brain-dedicated scanner (Neurofocus 810, whichis an upgrade of the Strichmann Medical Equipment) with afull-width at half maximum resolution of approximately6.5 mm, throughout the 20 cm field-of-view (http://www.neurophysics.com). After positioning of the subjects with thehead parallel to the orbitomeatal line, axial slices parallel andupward from the orbitomeatal line to the vertex wereacquired in 5 mm steps. Each acquisition consisted ofapproximately 1213 slices with 5 min scanning time perslice, acquired in a 6464 matrix. The energy window wasset at 135190 keV. At the day of the imaging session, theparticipants were not allowed to consume coffee or alcoholbecause they have been associated with altered striatal DArelease [26]. The first scan was obtained in the absence ofpharmacological intervention (baseline scan), on the first dayof the study (D1). The second and third scans wereperformed after DA depletion induced by oral administrationof AMPT, as described previously. Thus, three measures ofstriatal D2R binding were obtained in each subject: atbaseline (D1), in the short session (D2) after 1,500 mg ofAMPT and in the prolonged depleted state (D3) after a body-weight-adjusted AMPT dose.

Image reconstruction and analysis

SPECT data were reconstructed and analyzed blind toclinical data by the same experienced investigator (J.B.).

Attenuation correction of all images was performed asearlier described [27]. Images were reconstructed in 3Dmode (http://www.neurophysics.com). For quantification, aregion-of-interest (ROI) analysis was performed. FixedROIs for the striatum and occipital cortex were used. Forthe right and left striatum and left and right occipital cortex,a template with irregular ROIs, according to the contour ofthe striatum and occipital cortex, was positioned on fourconsecutive axial slices with highest striatal activity.Individual variation required movement of the fixed ROIs,without changing size and shape, within the template foroptimal fitting. For the right occipital and left occipitalcortices, irregular ROIs were drawn in one template. Meanstriatal and mean occipital binding densities were averagedfrom right and left ROIs. BPND was calculated as the ratioof specific to non-specific activity (total activity in striatumminus activity in occipital cortex, divided by activity inoccipital cortex).

Prolactin

Blood samples were taken at D2T0, D2T3 and D2T6 at theshort scanning day and at D3T26 at the prolonged scanningday for determination of plasma PRL levels. The cannulawas flushed with NaCl 0.9% to ensure that the cannularemained open. PRL was measured by time-resolvedfluoroimmunoassay (DELFIA Prolactin, Wallac Oy, Turku,Finland). The samples were not run in one-assay run tomimic the real diagnostic procedure. The total assayvariation ranged from 5.87.6%.

Subjective well-being during depletion

To determine subjective well-being, the short version of theSWN [1820] (Dutch translation) was administered to thesubjects at baseline (D2T0) after the administration of1,500 mg AMPT (D2T6) and in the prolonged challengesession, 24 h after the first AMPT dose (D3T24). This scalewith six response categories covers 20 statements on fivesubscales (mental functioning, self-control, emotional reg-ulation, physical functioning, social integration).

Statistical analysis

Statistical analyses concerning the differences in BPND,SWN scores and PRL levels, at the different time points,were performed using the non-parametric Wilcoxon test forpaired samples. Spearmans rho correlation coefficientswere calculated to investigate the relationship betweenBPND, SWN scores and PRL levels. A probability value of0.05 two-tailed was selected as significance level. Statisticalanalyses were performed using the Statistical Package forthe Social Sciences (SPSS, release 12.0.1 for Windows).

1352 Eur J Nucl Med Mol Imaging (2008) 35:13501356

Results

Six healthy subjects completed the study. The age (mean standard deviation) of the subjects was 29.36.95 years,respectively. There were three women and three menincluded. None of the subjects smoked. After AMPTadministration, no serious adverse events like acutedystonia or crystalluria were present.

Striatal D2 binding

There was no significant difference in mean BPND bindingat baseline (D1) and 5 h after the administration of

1,500 mg AMPT (D2T5, Fig. 1). The relative change ofmean BPND compared to the baseline after a more prolongedchallenge state (D3T25) with a body-weight-adjusted AMPTdose ranged between 2.1% and 20.4% with a mean relativeincrease of 8.8%9.0%, which was statistically significant(n=6, p=0.046, Wilcoxon test for paired samples). In onlyone subject, the mean BPND was lower after the moreprolonged challenge procedure than at baseline. In allsubjects, the mean [123I]IBZM binding was higher in theprolonged challenge state compared to the short challengestate. There was a significant difference of mean BPNDbetween the short challenge D2T5 and the more prolongedchallenge D3T25 (p=0.028).

Prolactin

There was a significant increase (p=0.028) of mean PRLlevels from baseline (D2T0, n=6, 10.64.3 g/l) after theadministration of 1,500 mg AMPT at 3 h after the first drugintake (D2T3, n=6, 89.041.8 g/l; Fig. 2). The levelsdecreased subsequently at D2T6 (n=6, 47.218.3, p=0.028; compared with D2T3) in all subjects and stayedabove baseline values (p = 0.028). The PRL levels (n=4,37.812.6) after a body-weight-adjusted AMPT dose, 26 hafter the first drug intake (D3T26), were not significantlydifferent from baseline (p = 0.068). No correlations weredetected between D2R BPND and PRL levels.

Subjective well-being during dopamine depletion

SWN scores at baseline (D2T0) and after dopaminedepletion (D2T6, D3T24) are displayed in Fig. 3. Therewere no differences in SWN scores at baseline and after the

Fig. 1 Effect of alpha-methyl-para-tyrosine (AMPT) on the mean[123I]IBZM striatal dopamine D2 receptor (D2R)-binding potential(BPND). The D2R BPND was measured at baseline (D1T0), after theadministration of 1,500 mg AMPT at 5 h after the first drug intake(D2T5) and after 40 mg AMPT/kg body weight, 25 h after the firstdrug intake (D3T25). The mean D2R BPND after 40 mg AMPT/kg wassignificantly different from baseline (p=0.046) and D2T5 (p=0.028),Wilcoxon test for paired samples

Fig. 2 Mean plasma prolactin (PRL, g/l) levels after alpha-methyl-para-tyrosine (AMPT) administration. The plasma levels weremeasured at baseline (D2T0) after the administration of 1,500 mgAMPT at 3 h (D2T3) and 6 h (D2T6) after the first drug intake and after40 mg AMPT/kg body weight, 26 h after the first drug intake (D3T26).Error bars indicate SEM

Fig. 3 Effect of AMPT on subjective well-being as measured with theSWN. Mean SWN scores were measured at baseline (D2T0) after theadministration of 1,500 mg AMPT at 6 h after the first drug intake(D2T6) and after 40 mg AMPT/kg body weight, 24 h after the firstAMPT dose (D3T24). Error bars indicate SEM. mf mental functioning,er emotional regulation, pf physical functioning. Total and subscalespresented showed a significant AMPT effect, p

administration of 1,500 mg AMPT. After prolongeddopamine depletion, the mean total SWN scores droppedsignificantly (p = 0.028) by 31.527.6 points compared tothe baseline, indicating a worsening in subjective experi-ence. There was a significant decline of the subscalesmental functioning (p=0.043), emotional regulation (p=0.042) and physical functioning (p=0.043). No correlationswere detected between D2R BPND and SWN scores.

Discussion

In this study, we describe induction of acute monoaminedepletion with two alternative procedures to the commonAMPT procedure evaluated with [123I]IBZM SPECT usingrelatively low doses of AMPT. We found no change ofmean striatal [123I]IBZM BPND after the first and shortAMPT challenge compared to the baseline. However, thisstudy showed that AMPT administration (40 mg/kg bodyweight, over 25 h) induced a significant increase (+8.89.0%) in measured BPND in six healthy volunteers. Forinterpretation of the present work, the following issues mustbe considered.

The purpose of monoamine depletion paradigms is toinvestigate associations between the function of neuro-transmitters and neuropsychiatric disorders in humans. Theoriginal AMPT procedure in humans was based on theassumption of complete synaptic DA depletion [28]. Underthis assumption, the difference between [123I]IBZM SPECTscans before and after acute DA depletion provides ameasure of the proportion of striatal D2R occupied byendogenous DA at baseline. In this initial procedure,AMPT was selected as the depleting agent because thisdrug was approved for human use and because AMPTeffects are rapidly reversible. The dose and frequency toobtain DA depletion were based on findings from previousstudies. In these studies, it was found that doses exceeding1,000 mg daily result in an enzyme inhibition (tyrosinehydroxylase) of more than 50% and that stepwise incrementof dosages up to 1,500 mg per day produce markedincreases in inhibition of catecholamine production [29].Another study showed a decrease of the DA metabolitehomovanillic acid in cerebrospinal fluid with an intervalranging from 68% to 77% after 4,000 mg AMPT per day[30]. In these studies, it was also found that higher doses ofAMPT did not induce significantly more inhibition of theenzyme tyrosine hydroxylase [13, 28]. With a half-life ofabout 4 h and a peak plasma concentration of about 2 hafter oral administration, the ingestion of AMPT every 6 hfor 2 days was expected to provide suitable plasmaconcentrations at steady state. Therefore, in the originalAMPT procedure, a total dose of 8,000 mg AMPT over2 days (1 g every 6 h) was administered orally. As in this

study, the subjects presented extrapyramidal symptoms andas 80% D2R blockade is expected to provoke thesesymptoms, depletion was suggested in the 70% to 80%range [28].

As a lot of adverse effects were reported in the firstdepletion studies, Verhoeff et al. [17] reduced the totalamount of administered AMPT to 4,500 mg over 28 h.Using PET and the radioligand [11C]raclopride, AMPTresulted in significant increase in D2R BP with a magnitudecomparable with earlier findings, suggesting comparablechanges in striatal DA concentration with lower AMPTdoses. Ever since, administered AMPT dosages in neuro-imaging challenge studies have been about 4,500 mg over2 days. Nevertheless, though the following studies did notadminister the total dose of 8,000 mg AMPT, side effectsand study withdrawal were still a dilemma [14].

The occurrence of side effects due to these relativelyhigh doses (4,500 to 8,000 mg) and the knowledge thatAMPT does not completely block tyrosine hydroxylase [13,28] raise the question of the necessity of maximum DAdepletion to study the dysregulation of the DA system. Webelief that a depletion paradigm is equally valuable toinvestigate whether patients with different neuropsychiatricdisorders differ in the response to an adequate DAchallenge. This requires that the effect of AMPT on striatal[123I]IBZM BPND should at least be significant and reliable.

Although the magnitude of the AMPT-induced change ofstriatal [123I[IBZM BPND in our sample is small, the changeis significant. Moreover, our findings are in accordancewith the findings of an IBZM SPECT study that showed asignificant AMPT effect on mean striatal BPND (+9%7%)in a sample of 18 healthy subjects with comparable meanage (318 years), receiving a total dose of 8,000 mgAMPT, over 48 h [5]. Besides, studies have demonstratedthat the between-study variability in the AMPT effect ingeneral is quite large. For example, in other PET andSPECT studies in healthy subjects, with 4,0008,000 mgAMPT over 48 h, mean differences in striatal D2R BPNDranged from +13% to +28% [17, 28, 31, 32]. The between-subject variability in the present study is large as well(ranges from 2.1% and 20.4%), which is also in agreementwith findings by others. It has to be taken into account thatthese studies did not employ the same instrumentation andmethodology. However, to our best knowledge, testretestvariability using the bolus plus constant infusion paradigmwith IBZM SPECT after AMPT challenge has not beenreported yet. Therefore, similarities and differences in theAMPT effect in the mentioned studies should be interpretedwith caution.

Thus, our data suggest that, to induce acute DAdepletion to measure acute changes in striatal synaptic DAconcentration in vivo, this procedure with relative lowdoses of AMPT is a suitable alternative to the common

1354 Eur J Nucl Med Mol Imaging (2008) 35:13501356

AMPT procedure. The probability of side effects and studywithdrawal can be reduced by this procedure. However, it isuncertain if the magnitude of striatal DA depletion achievedby this regimen is equally sufficient to demonstratedysfunction of neurotransmitters in neuropsychiatric disor-ders as the original AMPT procedure. Future studies usingthis paradigm in psychiatric populations should address thisissue. Moreover, although our present results (particularlythe results obtained with the AMPT challenge adjusted forbodyweight) suggest that we induced a significant reduc-tion of DA concentrations, including striatal synaptic DA,we do not know the extent of this reduction. As we did notobserve extrapyramidal side effects, striatal DA depletionmay be less than 7080%. Additional studies are needed toestimate the actual depletion of striatal DA concentrations,which could be induced with this novel procedure. To doso, it might be of value to measure plasma AMPT levels inhumans and induce comparable plasma levels in smalllaboratory animals. In the same animal experiment, micro-dialysis can be performed to assess the actual extracellularstriatal DA concentrations. Although such a strategy can beused to estimate the effects on extracellular DA levels, itdoes not reflect changes on the synaptic level (for adiscussion, see Schiffer et al. [33]). Alternatively, onemay estimate the depletion by measures of the predominantDA metabolite homovanillic acid (HVA) in cerebrospinalfluid in humans, but it is expected that the magnitude of DAdepletion is larger than HVA depletion [5].

In agreement with previous studies applying the AMPTparadigm in healthy volunteers [17, 29, 34, 35], AMPTadministration increased serum PRL levels significantlyshortly after its first administration, and PRL levels fellthereafter, even though more AMPT was administered.AMPT-induced DA depletion consistently produced a two-to ninefold increase in PRL levels [17, 29, 34, 35].Previously, PRL has been used as a marker of theeffectiveness of AMPT as an inhibitor of endogenous DAsynthesis [35] because hypothalamic DA is known toinhibit PRL release at the level of the pituitary gland [36].However, DA is not the only factor controlling PRL levels,and there is no direct relation between hypophysial stalkDA levels and serum PRL levels [36]. Thus, our findings,taken together with the results from the mentioned studies,suggest that, though an initial PRL response indicates acuteDA depletion, it may not be a useful indicator of theadequacy of DA depletion in striatum.

Subjective experience worsened in the prolonged proce-dure, with effect on mental functioning, emotional regula-tion and physical functioning, as measured by the SWNscale. From studies with antipsychotics, we know thatantagonism of dopaminergic neurotransmission is relevantfor subjective experience, and higher striatal D2R occu-pancy by antipsychotics is related to worse subjective

experience [37]. These type of subjective side effects havebeen labeled as neuroleptic dysphoria [38] or neuroleptic-induced anhedonia [20]. In addition, subjective well-beingduring antipsychotic medication is associated with medica-tion compliance [37], and discomfort is reason for studywithdrawal in AMPT challenge studies [5, 39]. Thus,although a relatively low dose of AMPT was administered,subjective well-being worsened. Nevertheless, all thesubjects completed the study, in contrast to some otherAMPT challenge studies using higher AMPT doses.

The results of the present study should be interpreted inlight of the following considerations. The order of scanningand depletion was not randomized. Therefore, we cannotrule out a time or order effect. In addition, the sample sizeis limited; however, the effect exceeds p

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1356 Eur J Nucl Med Mol Imaging (2008) 35:13501356

AMPT-induced monoamine depletion in humans: evaluation of two alternative [123I]IBZM SPECT proceduresAbstractAbstractAbstractAbstractAbstractIntroductionMaterials and methodsSubjectsDepletion regimenSPECT protocolImage reconstruction and analysisProlactinSubjective well-being during depletionStatistical analysis

ResultsStriatal D2 bindingProlactinSubjective well-being during dopamine depletion

DiscussionReferences

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