Postweanling social isolation rearing produces long term changes in many behaviors, including increased locomotor novelty response, increased anxiety-like behavior, and increased ethanol consumption. In addition, isolates also show changes in dopaminergic activity, including increases in ventral tegmental dopamine neuron burst firing, increased accumbal dopamine, and increased dopamine turnover in the accumbens and amygdala. However, these previous studies are limited in that they do not reveal aspects of presynaptic terminal function. Fast scan cyclic voltammetry is a powerful tool for measuring presynaptic function due to its high temporal and spatial resolution. In the present study, we will investigate uptake rates and autoreceptor sensitivity as well as ethanol responsiveness in social isolation and group housing reared animals using voltammetry. We will be focusing on function within the nucleus accumbens and basolateral amygdala, as these areas believed to be important for ethanol's reinforcing properties.
The research proposed in this NRSA is significant as alcohol abuse is a major concern for public health and safety. Indeed, alcohol is reported as one of the most abused substances within the United States, representing ~40% of all admissions to drug abuse treatment facilities (SAMHSA, Treatment Episode Data Set, 2008). Because basic science research of alcohol abuse implements non-human animal models, it is important for translational purposes that these animal models somewhat reflect the disorder. For example, animal models of increased drinking may help elucidate the underlying neuronal substrates/mechanisms behind alcoholism. Rats raised in social isolation are a promising candidate for such a model. Similar to humans, socially isolated rats show increases in anxiety and impulsivity, that seemingly predict alcohol consumption levels. Dopamine's putative role in ethanol reinforcement, make it a prime candidate for studying the neural correlates of alcohol abuse. By studying the dopamine systems of these animals, we may gain important insight into underlying mechanisms that increase an animal's propensity to drink. This research is clinically relevant in that it may help direct the development of new drugs for treating alcoholism.
|Yorgason, Jordan T; Ferris, Mark J; Steffensen, Scott C et al. (2014) Frequency-dependent effects of ethanol on dopamine release in the nucleus accumbens. Alcohol Clin Exp Res 38:438-47|
|Ferris, Mark J; Calipari, Erin S; Yorgason, Jordan T et al. (2013) Examining the complex regulation and drug-induced plasticity of dopamine release and uptake using voltammetry in brain slices. ACS Chem Neurosci 4:693-703|