Pharmacological challenge and synaptic response – assessing dopaminergic function in the rat striatum with small animal single-photon emission computed tomography (SPECT) and positron emission tomography (PET)
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Susanne Nikolaus
Abstract
Disturbances of dopaminergic neurotransmission may be caused by changes in concentrations of synaptic dopamine (DA) and/or availabilities of pre- and post-synaptic transporter and receptor binding sites. We present a series of experiments which focus on the regulatory mechanisms of the dopamin(DA)ergic synapse in the rat striatum. In these studies, DA transporter (DAT) and/or D2 receptor binding were assessed with either small animal single-photon emission computed tomography (SPECT) or positron emission tomography (PET) after pharmacological challenge with haloperidol, L-DOPA and methylphenidate, and after nigrostriatal 6-hydroxydopamine lesion. Investigations of DAT binding were performed with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ([123I]FP-CIT). D2 receptor bindingd was assessed with either [123I](S)-2-hydroxy-3-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide ([123I]IBZM) or [18F]1[3-(4′fluorobenzoyl)propyl]-4-(2-keto-3-methyl-1-benzimidazolinyl)piperidine ([18F]FMB). Findings demonstrate that in vivo investigations of transporter and/or receptor binding are feasible with small animal SPECT and PET. Therefore, tracers that are radiolabeled with isotopes of comparatively long half-lives such as 123I may be employed. Our approach to quantify DAT and/or D2 receptor binding at baseline and after pharmacological interventions inducing DAT blockade, D2 receptor blockade, and increases or decreases of endogenous DA concentrations holds promise for the in vivo assessment of synaptic function. This pertains to animal models of diseases associated with pre- or postsynaptic DAergic deficiencies such as Parkinson’s disease, Huntington’s disease, attention-deficit/hyperactivity disorder, schizophrenia or drug abuse.
©2011 by Walter de Gruyter Berlin Boston
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- Guest Editorial
- The emerging discipline of behavioral neuroimaging
- Special Issue: Behavioral Neuroimaging
- Cognition in action: imaging brain/body dynamics in mobile humans
- Neuroimaging for drug addiction and related behaviors
- Pharmacological challenge and synaptic response – assessing dopaminergic function in the rat striatum with small animal single-photon emission computed tomography (SPECT) and positron emission tomography (PET)
- Integrating PET with behavioral neuroscience using RatCAP tomography
- Motion-tracking technique in unrestrained small-animal single-photon emission computed tomography
- Functional magnetic resonance imaging in awake animals
- Manganese enhanced MRI (MEMRI): neurophysiological applications
- Optical detection of brain function: simultaneous imaging of cerebral vascular response, tissue metabolism, and cellular activity in vivo
Articles in the same Issue
- Guest Editorial
- The emerging discipline of behavioral neuroimaging
- Special Issue: Behavioral Neuroimaging
- Cognition in action: imaging brain/body dynamics in mobile humans
- Neuroimaging for drug addiction and related behaviors
- Pharmacological challenge and synaptic response – assessing dopaminergic function in the rat striatum with small animal single-photon emission computed tomography (SPECT) and positron emission tomography (PET)
- Integrating PET with behavioral neuroscience using RatCAP tomography
- Motion-tracking technique in unrestrained small-animal single-photon emission computed tomography
- Functional magnetic resonance imaging in awake animals
- Manganese enhanced MRI (MEMRI): neurophysiological applications
- Optical detection of brain function: simultaneous imaging of cerebral vascular response, tissue metabolism, and cellular activity in vivo
