Functional magnetic resonance mapping of intracerebroventricular infusion of a neuroactive peptide in the anaesthetised rat

Study-level wavelet cluster analysis and data-driven signal models in pharmacological MRI

“…Whereas in fMRI experiments the block-or event-related experimental paradigm is convolved with a haemodynamic response function (HRF) to provide a signal model (Friston, 1996), phMRI analysis within a GLM framework must contend with the fact that the experimental 'paradigm' of a single injection point under-informs the specification of a signal model that captures the full dynamic of signal changes. The simplest, and to date the most widely used, regressor has been a postinjection 'boxcar' step function (Dixon et al, 2005;Gozzi et al, 2005;Ireland et al, 2005;Lowe et al, 2002;Schmidt et al, 2006;Schwarz et al, 2004a;Shah et al, 2004;Shoaib et al, 2004;Skoubis et al, 2006;Thongsaard et al, 2005). This is a reasonable choice in the case of sustained signal changes, but may not provide a close match to the temporal profile when the response dynamics are more rapid.…”

Enhanced Prospects for Drug Delivery and Brain Targeting by the Choroid Plexus–CSF Route

“…Functional magnetic resonance mapping of neuroactive agents (e.g., the metabolically stable and potent NK1 receptor agonist GR-73632) introduced i.c.v. demonstrates rapid changes in the regional blood volumes of the amygdala, caudate putamen, and cortex (41). Thus, Bpharmacological MRI^lends support to the paradigm that CSF-borne drugs exert effects on metabolism/ blood flow in brain regions distant from the ventricles.…”

Methodological considerations in rat brain BOLD contrast pharmacological MRI

“…injection of cocaine in the conscious, restrained rat. In order to eliminate factors other than the drug itself causing phMRI responses, appropriate controls showed relatively little or no effect of control injection, that the drug effect was distal from the site of injection and that the drug was given at a psychoactive dose (Bui et al 1997;Febo et al 2004;Gozzi et al 2005). Furthermore, distribution time of the drug by i.c.v.…”

“…I.c.v. injections during phMRI experiments are of particular importance when administering a drug with low BBB permeability, such as neuroactive peptides (Gozzi et al 2005).…”

“…This method provides measurements of relative cerebral blood volume (rCBV), which is coupled to BOLD, and can increase the sensitivity of fMRI relative to BOLD with a reduction in vascular artefacts Chen et al 2001). This approach has been used to investigate the rCBV phMRI response to drugs such as cocaine Marota et al 2000;Schwarz et al 2004b), amphetamine and a D3 receptor antagonist (Chen et al 2001;Schwarz et al 2004a), bicuculline (Reese et al 2000;Abo et al 2004), 5-HT receptor ligands (Scanley et al 2001) and neuropeptides (Gozzi et al 2005) and has been used to study dopamine receptor supersensitivity following intranigral lesions (Nguyen et al 2000).…”