Impulsivity biomarkers
One of the most well-characterised measures of impulsive action is that obtained from the five-choice serial reaction time task, where premature motor responses made before a cue light is illuminated are classified as impulsive. Drugs which target different neurotransmitter systems (5-HT, dopamine and noradrenaline) can exert similar effects on this form of motor impulsivity suggesting that these neurochemicals interact in their modulation of impulse control. This could happen at the receptor level, such that activation of 5-HT receptors located on dopaminergic neurons can modulate the dopaminergic contribution to impulsivity, but also at the molecular level in that activation of different receptors could activate similar intracellular signaling cascades. We have recently found that the noradrenergic drug yohimbine also increases premature (impulsive) responding on this task, in keeping with clinical reports that yohimbine increases motor impulsivity in healthy volunteers. This compound also increases phosphorylation (activation) of the transcription factor CREB and the kinase ERK 42/44, which is upstream of CREB, within a specific region of the frontal cortex. The hypothesis that activation of CREB may be involved in yohimbine’s effects on impulsivity is supported by our findings that increasing levels of CREB in this area of frontal cortex also increases impulsivity and potentiates the actions of yohimbine.
We now want to determine whether changes in CREB and ERK signaling are common to other pharmacological manipulations which affect impulsivity, and whether a causal relationship can be established between molecular activation and the behavioural effects of drug administration. This could lead to the generation of a molecular footprint for compounds capable of modulating impulsivity, regardless of their pharmacological properties. This novel research could provide valuable insight into the nature of impulsive behaviour and potentially indicate novel therapeutic targets for impulse control disorders. Such research incorporates qPCR and Western blotting techniques to track changes in levels of different proteins and gene products through a molecular signalling pathway.
For more information, email info@winstanleylab.com with “Impulsivity Biomarkers” in the subject heading.