Microdialysis and SPECT measurements of amphetamine-induced dopamine release in nonhuman primates

✍ Scribed by Marc Laruelle; Raj N. Iyer; Mohammed S. Al-Tikriti; Yolanda Zea-Ponce; Robert Malison; Sami S. Zoghbi; Ronald M. Baldwin; Hank F. Kung; Dennis S. Charney; Paul B. Hoffer; Robert B. Innis; Charles W. Bradberry

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 151 KB
• Volume: 25
• Category: Article
• ISSN: 0887-4476
• DOI: 10.1002/(sici)1098-2396(199701)25:1<1::aid-syn1>3.0.co;2-h

✦ Synopsis

The competition between endogenous transmitters and radiolabeled ligands for in vivo binding to neuroreceptors might provide a method to measure endogenous transmitter release in the living human brain with noninvasive techniques such as positron emission tomography (PET) or single photon emission computerized tomography (SPECT). In this study, we validated the measure of amphetamine-induced dopamine release with SPECT in nonhuman primates. Microdialysis experiments were conducted to establish the dose-response curve of amphetamine-induced dopamine release and to document how pretreatment with the dopamine depleter alpha-methylpara-tyrosine (aMPT) affects this response. SPECT experiments were performed with two iodinated benzamides, [ 123 I]IBZM and [ 123 I]IBF, under sustained equilibrium condition. Both radiotracers are specific D 2 antagonists, but the affinity of [ 123 I]IBZM (K D 5 0.4 nM) is lower than that of [ 123 I]IBF (K D 5 0.1 nM). With both tracers, we observed a prolonged reduction in binding to D 2 receptors following amphetamine injection. [ 123 I]IBZM binding to D 2 receptors was more affected than [ 123 I]IBF by high doses of amphetamine, indicating that a lower affinity increases the vulnerability of a tracer to endogenous competition. With [ 123 I]IBZM, we observed an excellent correlation between reduction of D 2 receptor binding measured with SPECT and peak dopamine release measured with microdialysis after various doses of amphetamine. Pretreatment with aMPT significantly reduced the effect of amphetamine on [ 123 I]IBZM binding to D 2 receptors, confirming that this effect was mediated by intrasynaptic dopamine release. Together, these results validate the use of this SPECT paradigm as a noninvasive measurement of intrasynaptic dopamine release in the living brain.