Examining the effects of cocaine on Neurexin and Neuroligin levels in brain regions
Neurexins and neuroligins are proteins that are found in the membranes of neurons which are essential for forming and regulating synapses between neurons, including interactions with dopaminergic synapses, through interactions with each other. Specifically, neurexins reside on presynaptic neurons, while neuroligins reside on postsynaptic neurons. Imbalances in the presence of both neurexins and neuroligins have found to be correlated with a variety of increased rates of substance use in human genetic studies, as well as links to neurological disorders. In this project cocaine sensitization in relation to the presence of these proteins was focused on to examine the kind of effects it would have on it. This is because in the past 10 years there has been an over 200% increase in cocaine-involved overdose deaths, with ~5.2 million people aged 12+ in 2020 reporting cocaine use. Cocaine increases dopamine in the brain through blocking its reuptake from the synapse through the dopamine transporters. This build up of cocaine is what results in it producing a variety of lethal health abnormalities in the body. Cocaine is also associated with many changes to structural and functional plasticity in the brain. For example, cocaine is known to alter synaptic strength in the nucleus accumbens brain region. As such, although neurexins and neuroligins are known to play a significant role in synaptic plasticity, little is currently known about their potential to be regulated by the effects of cocaine and its related reward pathways, nor about how they themselves regulate cocaine. Though it can be expected that because of the build up of dopamine in the synapse, the brain will attempt to compensate for the increased levels by increasing synaptic structure molecules such as proteins to help with stabilization. From this the proposal's hypothesis was that with cocaine sensitization, there would be an increase in neurexin and neuroligin expression in the nucleus accumbens brain region, which will also have an impact on other physiological functions.