This proposal is a request for a Mentored Research Scientist Development Award (K01). This research plan is designed to allow me to develop my neurochemical research skills and maintain my productivity in the behavioral/developmental aspects of alcohol drinking behavior. Successful completion of this proposal will further strengthen my potential as a productive researcher within the field of alcohol. The overall objectives of this proposal are to determine neurobiological factors involved in promoting high alcohol drinking behavior in the young and to determine some long-range consequences of adolescent alcohol drinking. The hypotheses to be tested are that (1) neurobiological factors associated with excessive alcohol drinking in adults are also present early in life and contribute to high alcohol consumption in the young and (2) chronic ethanol drinking during the adolescent period produces unique and enduring neurochemical changes. These hypotheses will be tested using animal models, i.e., lines of rats selectively bred for their disparate alcohol drinking characteristics. Male and female alcohol-preferring P and alcohol-non preferring NP rats, as well as heterogeneous Wistar rats, will be used in these studies. The first specific aim will determine if there are differences in the serotonin (5-HT) and dopamine (DA) systems between P, NP and Wistar rats at the age of onset of alcohol drinking (a) using HPLC-EC analysis to measure the regional CNS contents of 5-HT, DA and their metabolites in animals at 15, 25 and 35 days of age and (b) quantitative autoradiography procedures to determine the regional densities of 5-HT21 sites and 5-HT, sites at 25 days of age. The second specific aim will examine, using in vivo microdialysis, the effects of chronic adolescent alcohol drinking by the P rat on the response of the VTA DA and raphe 5-HT systems to a challenge dose of ethanol. The third specific aim will determine if there are innate functional differences in the DA and 5-HT systems and if physiological factors associated with alcohol drinking in adult. (e.g., tolerance development and low-dose stimulatory effects of ethanol) are also present at the age of onset of alcohol drinking. Information gained from this proposal will provide greater insight into neurobiological factors involved in adolescent alcohol drinking and if access to ethanol during development produces long-term consequences.
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| McBride, W J; Chernet, E; McKinzie, D L et al. (1998) Quantitative autoradiography of mu-opioid receptors in the CNS of alcohol-naive alcohol-preferring P and -nonpreferring NP rats. Alcohol 16:317-23 |
| McKinzie, D L; Chen, W J; Spear, N E (1998) Ontogenetic differences in the expression of conditioned stimulus conditioning: effects of retention interval. Behav Neurosci 112:920-8 |
| Zhou, F C; McKinzie, D L; Patel, T D et al. (1998) Additive reduction of alcohol drinking by 5-HT1A antagonist WAY 100635 and serotonin uptake blocker fluoxetine in alcohol-preferring P rats. Alcohol Clin Exp Res 22:266-9 |
