Differential effects of the d- and l- isomers of amphetamine on pharmacological MRI BOLD contrast in the rat

Abstract

Rationale The D-and L-amphetamine sulphate isomers are used in the formulation of Adderall XR®, which is effective in the treatment of attention-deficit hyperactivity disorder (ADHD). The effects of these isomers on brain activity has not been examined using neuroimaging. Objectives This study determines the pharmacological magnetic resonance imaging blood-oxygenation-level-dependent (BOLD) response in rat brain regions after administration of each isomer. Materials and methods Rats were individually placed into a 2.35 T Bruker magnet for 60 min to achieve basal recording of variation in signal intensity. Either saline (n=9), D-amphetamine sulphate (2 mg/kg, i.p.; n=9) or L-amphetamine sulphate (4 mg/kg, i.p.; n=9) were administered, and recording continued for a further 90 min. Data were analysed for BOLD effects using statistical parametric maps. Blood pressure, blood gases and respiratory rate were monitored during scanning. Results The isomers show overlapping effects on the BOLD responses in areas including nucleus accumbens, medial entorhinal cortex, colliculi, field CA1 of hippocampus and thalamic nuclei. The L-isomer produced greater global changes in the positive BOLD response than the D-isomer, including the somatosensory and motor cortices and frontal brain regions such as the orbitofrontal cortices, prelimbic and infralimbic cortex which were not observed with the D-isomer. ConclusionsThe amphetamine isomers produce different BOLD responses in brain areas related to cognition, pleasure, pain processing and motor control probably because of variations on brain amine systems such as dopamine and noradrenaline. The isomers may, therefore, have distinct actions on brain regions affected in ADHD patients.

Peculiar response to methylphenidate in adolescent compared to adult rats: a phMRI study

“…Nevertheless, anaesthesia in rodent MRI studies is sometime necessary, especially when scanning duration takes longer than 2 h. Inhalation anaesthetics are widely used in phMRI studies (Abo et al 2003;Hewitt et al 2005;Shoaib et al 2004;Sicard et al 2003;Sicard and Duong 2005). Isoflurane is widely used because it produces stable anaesthesia over a prolonged period of time, with minimal physiological alterations (Easton et al 2007a;Easton et al 2007b). In our present study, we cannot discard the possibility that the observed BOLD profiles are due to combined effects of both MPH plus the anaesthetic.…”

Detection of Visual Activation in the Rat Brain Using 2-deoxy-2-[18F]fluoro-d-glucose and Statistical Parametric Mapping (SPM)

“…Few studies have used SPM techniques in rats with different imaging modalities: autoradiographic iodoantipyrine [30][31][32][33][34], fMRI [35][36][37][38][39][40], and FDG-PET [20,41,42]. Two PET studies used a standardization according to a custom digital template matched to a highresolution microMRI image in Paxinos orientation [41,42].…”

Fragmentation pathways and differentiation of positional isomers of sorafenib and structural analogues by ESI‐IT‐MSn and ESI‐Q‐TOF‐MS/MS coupled with DFT calculations

“…Sorafenib inhibits tumor cell proliferation and tumor cell vacularisation through activating the receptor tyrosine kinase signaling RAS/RAF/MEK/ERK cascade pathway . Sorafenib is often obtained by over 4 steps of chemical synthesis, and the intermediates and side products including the positional pattern of substituents are usually the main potential impurities which may influence quality, efficacy, and safety of final products . The international conference on harmonization of technical requirements for registration of pharmaceuticals of human use (ICH) recommends that the amounts of impurities are limited to less than 0.1% .…”