Summary
The radioligand [123I]β-CIT binds to dopamine transporters in striatum and to serotonin transporters in brainstem. Endogenous dopamine or serotonin may compete with radiol igand binding at monoamine transporters.
We used α-methyl-p-tyrosine (AMPT) to block dopamine production and measured [123I]β-CIT binding before and after endogen ous dopamine was restored by IV admini stration of the dopamine precur sor L-dihydroxyphenylalanine (L-DOPA) in rhesus monkey s. P-chlorophenylalanine (pCPA) was used to inhibit serotonin production, and [123I]β-CIT binding was assessed before and after IV admini stration of the serotonin precursor 5-hydroxy-L-tryptophan (L-5-HTP) restored endogenous serotonin. Pretreatment with benserazide blocked peripheral decarboxylization in both paradigms.
Serotonin restoration measurably displaced [123I]β-CIT binding to brainstem serotonin transporters but not to striatal dopamine transporters. Restoration of dopamine apparently did not affect [123I]β-CIT binding to striatal dopamine transporters. However, dopamine restoration reduced radioligand bindin g to brainstem serotonin transporters, most likely due to dopamine relea se from serotonin neurons following L-DOPA administration.
The higher striatal density of dopamine transporters relative to dopamine concentrations may explain why [123I]β-CIT displacement by endogenous dopamine was not observed. This study indicate s that [123I]β-CIT binding in brainstem (raphe area) is affected by endogenous serotonin release in vivo and that L-DOPA treatment may cause serotonin neurons in the brainstem to corelease dopamine.
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References
Abi-Dargham A, Rodenhiser J, Printz D, Zea-Ponce Y, GiI R, Kegeles LS, Weiss R, Cooper TB, Mann JJ, Van Heertum RL, Gorman JM, Laruelle M (2000) Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. Proc Natl Acad Sci USA 97: 8104–8109
Baldwin RM, Zea-Ponce Y, Zoghbi SS, Laruelle M, AI-Tikritti MS, Sybirska EH, Malison RT, Neumeyer JL, Milius RA, Wang S, Stabin M, Smith EO, Chamey DS, Hoffer PB, Innis RB (1993) Evaluation of the monoamine uptake site ligand [123I]methyl-3β-(Iodophenyl)tropane-2β-carboxylate ([123I]β-CIT) in non-human primates: pharmacokinetics, biodistribution and SPECT brain imaging coregistered with MRI. Nucl Med Biol 5: 597–606
Carboni E, Tanda GL, Frau R, Dichiara G (1990) Blockade of the noradrenaline carr ier increases extracellular dopamine concentrations in the prefrontal cortex-evidence that dopamine is taken up in vivo by noradrenergic terminals. J Neurochem 55: 1067–1070
Ferre S, Artigas F (1993) Dopamine D2 receptor-mediated regulation of serotonin extracellular concentration in the dorsal raphe nucleus of freely moving rats. J Neurochem 61: 772–775
Fisher RE, Morris ED, Alpert NM, Fischman AJ (1995) In vivo imaging of neuromodulatory synaptic transmission using PET: a review of relevant neurophysiology. Hum Brain Map 3: 24–34
Giros B, Wang YM, Suter S, Mcleskey SB, Pift C, Caron MG (1994) Delineation of discrete domains for substrate, cocaine, and tricyclic antidepressant interactions using chimeric dopamine-norepinephrine transporters. J BioI Chem 269: 15985–15988
Gradwell PB, Everitt BJ, Herbert J (1975) 5-hydroxytryptamine in the central nervous system and sexual receptivity of female rhesus monkeys. Brain Res 88: 281–293
Heinz A, Higley JD, Jones DW, Gorey JG, Hommer D, Saunders R, Zajicek K, Suorni SS, Knable MB, Lesch KP, Weinberger DR, Linnoila M (1998) In vivo association between brainstem serotonin transporters and sensitivity to alcohol intoxication.Am J Psychiatry 155: 1023–1028
Heinz A, Saunders RC, Kolachana BS, Bertolino A, Jones DW, Gorey JG, Bachevalier J, Lee KS, Knable MB, Saunders RC, Weinberger DR (1999) Disinhibition of subcortical dopaminergic neurotransmission in rhesus monkeys with neonatal mesial temporal lesions. Synapse 39: 71–79
Heinz A, Jones DW, Gorey IG, Bennet A, Suomi SI, Weinberger DR, Higley ID (2003) Serotonin tran sporter availability correlates with alcohol intake in non-human primates. Mol Psychiatry 8: 231–234
Jagust Wl, Eberling JL., Biegon A, Taylor SE, Van Brocklin HF, Jordan S, Hanrahan SM, Roberts JA, Brennan KM, Mathis CA (1996) Iodine-123-5-iodo-6-nitroquipazine: SPECT radiotracer to image the serotonin transporter. J Nucl Med 37: 1207–1214
Laruelle M, Baldwin RM, Malison RT, Zea-Ponce Y, Zoghbi SS, AI-Tikriti MS, Sybirska MH, Zimmermann RC, Wiesniewski G, Neumeyer JL, Milius RA, Wang S, Smith EO, Roth RH, Charney DS, Hoffer PB, Innis RB (1993) SPECT imaging of dopamine and serotonin tran sporters with [123I]β-CIT: pharmacological characterization of brain uptake in nonhuman primates. Synapse 13: 295–309
Laruelle M, Wallace E, Seibyl lP, Baldwin RM, Zea-Ponce Y, Zoghbi SS, Neumeyer JL, Charney DS Hoffer PB, Innis RB (1994) Graphical, kinetic, and equilibrium anal yses of in vivo [123I]β-CIT binding to dopamine tran sporters in healthy human subjects. J Cereb Blood Flow Metab 14: 982–994
Malison RT, Price LH, Berman R, van Dyck CH, Pelton GH, Carpenter L (1998) Reduced brain serotonin transporter availability in major depression as mea sured by [123I]-2β-carboxy-3β-(4-iodophenyl)tropane and single photon emission computed tomography. Biol Psychiatry 44: 1090–1098
Martin-Ruiz R, Ugedo L, Honrubia MA, Mengod G, Artigas F (2001) Control of serotonergic neurons in rat brain by dopaminergic receptors outside the dorsal raphe nucleus. J Neurochem 77: 762–775
Moron JA, Brockington A, Wise RA, Rocha BA, Hope BT (2002) Dopamine uptake through the norepinephrine tran sporter in brain regions with low levels of the dopamine transporter: evidence from knock-out mouse lines. J Neurosci 22: 389–395
Pan Y, Gembom E, Peng W, Lesch K-P, Mossner R, Simantov R (2001) Plasticity in serotonin uptake in primary neuronal cultures of serotonin tran sporter knockout mice. Dev Brain Res 126: 125–129
Pirker W, Asenbaum S, Kasper S, Waiter H, Angelberger P, Koch G, Pozzera A, Deecke L, Podreka I, Bruecke T (1995) β-CIT SPECT demonstrates blockade of 5HT-uptake sites by citalopram in the human brain in vivo. J Neural Transm 100: 247–256
Pirker W, Asenbaum S, Hauk M, Kandlhofer S, Tauscher J, Willeit M (2000) Imaging serotonin and dopamine tran sporters with 123I-β-CIT SPECT: binding kinetics and effects of normal aging. J Nucl Med 41: 36–44
Rinne JO, Kuikka JT, Bergström KA, Rinne UK (1995) Striatal dopamine tran sporter in different disability stages of Parkinson’s disea se studied with [123]β-CIT SPECT. Parkinsonism Rel Dis 1: 47–51
Seibyl JP, Wallace E, Smith EO, Stabin M, Baldwin RM, Zoghbi SS, Zea-Ponce Y, Gao Y, Zhang WY, Neumeyer JL, Zubal IG, Charney DS, Hoffer PB, Innis RB (1994 ) Whole-body biodi stribution, radiation absorbed dose and brain SPECT imaging with Iodine-I23-β-CIT in healthy human subjects. J Nucl Med 35: 764–770
Suarez-Roca H, Cubeddu LX (2002) The selective serotonin reuptake inhibitor citalopram induces the storage of serotonin in catecholaminergic terminals. J Pharmacol Exp Ther 302: 174–179
Torres GE, Gainetdinov RR, Caron MG (2003) Plasma membrane monoamine transporters: Structure, regulation and function. Nat Rev Neurosci 4: 13–25
Zhou FC, Lesch K-P, Murphy DL (2002) Serotonin uptake into dopamine neurons via dopamine transporters: a compensatory alternative. Brain Res 942: 109–119
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Heinz, A. et al. (2004). Depletion and restoration of endogenous monoamines affects β-CIT binding to serotonin but not dopamine transporters in non-human primates. In: Müller, T., Riederer, P. (eds) Focus on Extrapyramidal Dysfunction. Journal of Neural Transmission. Supplementa, vol 68. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0579-5_4
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DOI: https://doi.org/10.1007/978-3-7091-0579-5_4
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