Alcohol abuse and alcoholism are major health problems that cost our society numerous lives and billions of dollars each year. Understanding how alcohol can come to control an individual's behavior is key to the development of effective treatment. Our research program has begun to identify specific brain regions, and chemicals in these regions, that are involved in regulating how much alcohol an individual will consume. The region of the brain known as the hypothalamus controls most of the body's regulatory processes, such as feeding, drinking, and mating. For instance, it has been shown that direct injections of the neurotransmitter noradrenaline into this area will increase carbohydrate intake and result in obesity (serotonin has the opposite effect) in rats. Obesity, like alcoholism, involves the excessive consumption of a substance. Thus, the hypothesis of these studies is that alcohol may result in excessive intake by usurping the brain is natural feeding and drinking mechanisms which can result in a loss of control. The operant self-administration technique is considered to be one of the most valid measures of alcohol-seeking behavior. When combined with CNS microinjection techniques, the role of specific brain regions and receptor systems can be characterized.
Three specific aims are proposed to characterize the involvement of hypothalamic regulatory systems in alcohol-seeking behavior.
Specific Aim I will characterize the role of noradrenergic receptors located in the paraventricular nucleus (PVN) of the hypothalamus in regulating alcohol and sucrose reinforced responding. These studies will be conducted in ethanol-experienced and ethanol-naive rats and will test whether alcohol experience shifts the function of the PVN from regulation of carbohydrate intake to the control of alcohol seeking behavior.
Specific Aim 2 will test the role of serotonin receptors, and Specific Aim 3 will test the influence of opiate receptors, in the same behavioral procedures. These studies will examine the degree to which the primary function of the PVN may be altered as a function of alcohol experience. The results from these studies will help clarify how homeostatic brain systems, such as the hypothalamus, may become involved in alcohol-seeking behavior.
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| Kelley, S P; Nannini, M A; Bratt, A M et al. (2001) Neuropeptide-Y in the paraventricular nucleus increases ethanol self-administration. Peptides 22:515-22 |
