RenaSci offers a range of neurochemical assays for investigating the ability of drugs to interfere with the synthesis, metabolism, release or reuptake of neurotransmitters in vitro or ex vivo. Examples include:
• 3H monoamine uptake in vitro
• Inhibition of monoamine oxidase A and B activity in mouse and rat brain in vitro
• Inhibition of 5-HT and noradrenaline turnover (5-HTP and MHPG formation) ex vivo
Clonidine reduces unconjugated MHPG, an indicator of
noradrenaline turnover, in rat and mouse brain
We also offer ‘neurochemical fingerprinting’ in mice, this is an ex vivo screen that discriminates between drugs with different presynaptic dopaminergic mechanisms. The model was validated by studying the effects of a variety of indirect dopamine mimetic drugs on levels of dopamine and its metabolites in the striatum and prefrontal cortex.
Neurochemical fingerprinting discriminates between drugs with
different presynaptic dopaminergic mechanisms
GBR 12909 is a dopamine reuptake inhibitor, d-amphetamine is a monoamine releasing agent, methylphenidate is a catecholaminergic stimulant, MK-801 is a NMDA receptor antagonist and tranylcypromine is an irreversible monoamine oxidase inhibitor. These drugs, which act via different presynaptic mechanisms, produce unique patterns of effects on dopamine and its metabolites in the striatum and prefrontal cortex, reflecting the different presynaptic regulation of dopamine release and metabolism in these two brain regions.
Ex vivo neurochemistry can, therefore, be used to characterise the effects of novel compounds on presynaptic dopaminergic function, and compare them to reference compounds, including drugs of abuse.
Neurochemical fingerprinting can be combined with an assessment of locomotor activity and stereotyped behaviour to profile the effects of drugs on limbic and striatal dopaminergic function and neurochemistry in the same mice.
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