Research Background

Research in the Cragg laboratory spans from neurodegenerative disorders to drug addiction. Our work focuses on understanding dopamine neurotransmission, particularly within the basal ganglia and reward-related processing centres. Signalling by the neurotransmitter dopamine in the striatum of the central nervous system is critical to the normal control of locomotion, motivation, rewards and habitual behaviours. In the brain’s neural representation of reward-related events, striatal dopamine is a neurochemical substrate that appears to encode reward predictions like conditioned reward-related stimuli as well as prediction errors or unexpected receipt of rewards. Furthermore, dopamine systems contain the pharmacological sites of action of substances of abuse including, nicotine, cocaine, amphetamines and opiates. Modification of synaptic dopamine signalling by these substances probably conveys reinforcing properties that ultimately gives rise to addictive abuse. In addition, degeneration or dysfunction of dopamine systems underlies key neuropathologies and psychiatric disorders including the motor disorder Parkinson’s disease, the psychomotor deficits of Tourette syndrome and schizophrenia. Clearly, insights into the mechanisms that govern dopamine signalling are essential if we are to understand the physiological functions of dopamine, the neurochemical effects of drugs of abuse, and ultimately, the clinical management of the addiction disorders and pathologies in which dopamine is critically involved.

Current research programme

We use real-time electrochemical and theoretical approaches to explore how dopamine signals are presynaptically controlled, to understand how dopamine encodes motor and reward-related functions and ultimately, to gain insight into therapeutic strategies for Parkinson’s disease and drug addiction.

Studies currently underway in the laboratory include:

1. the mechanisms through which drugs of abuse (e.g. nicotine, cocaine) modify short-term plasticity of release probability at dopamine synapses in vitro to ultimately govern drug reinforcement
2. the role of subtype-specific nicotinic cholinergic receptors in the regulation of dopamine signalling and therapeutic relevance to Parkinson’s disease and nicotine addiction
3. interactions between Parkinson’s related mutations in synucleins and dopamine signalling.

Wider areas of interest include somatodendritic neurotransmitter release, the synaptic regulation of related brain amines (serotonin, histamine) and extrasynaptic spillover signaling. 

Stephanie Cragg