Robert F. Smith, Ph.D. - US grants

animal developmental psychology; ethology; gestational age; lidocaine; embryo /fetus drug adverse effect; postnatal growth disorder; avoidance behavior; dosage; teratogens; drug administration routes; prenatal stress; behavior test; orientation; parent offspring interaction; conditioning;

Recent human data, and very limited animal data, suggest that cocaine useage in gestation is associated with adverse outcomes in the infant, including altered neurobehavioral development. Our laboratory has recently published data indicating that several postweaning behaviors are altered in rats exposed to 10 mg/kg/d cocaine in utero, and we have unpublished data indicating that this dose may alter hippocampal morphology of offspring. we now propose to establish a dose-effect curve for neurobehavioral effects of prenatal cocaine exposure, expand the range of behaviors tested, establish whether such effects persist when offspring are fostered to undosed surrogate dams, and further investigate neuroanatomical correlates of the altered behavior. Rats will be dosed during gestation with 5, 10, 20, or 40 mg/kg/d cocaine; controls will include uninjected and injected/pairfed controls. All pups will be fostered to undosed surrogates at birth. Offspring will be evaluated on a number of different measures of behavioral development and adult behavior (including representatives of each category suggested for testing by the Collaborative Behavioral Teratology Study), and on several aspects of hippocampal neuromorphology. The proposed work will expand the body on data on neurobehavioral effects of prenatal cocaine exposure (particularly on effects in adult offspring), and will provide a basis for continuing, more detailed studies on mechanisms of prenatal cocaine in our laboratory.

DESCRIPTION: (Applicant's Abstract) Although studies with humans confirm that there is a typical progression from tobacco and alcohol through marijuana to other drugs such as cocaine and heroin (the "gateway" hypothesis), no data exist on whether this is a purely social phenomenon, or whether there are underlying neurobiological substrates for this drug progression. Recent work on common substrates for different addictive drugs, and on drug interactions, make it plausible that there may be a biological component to drug progression. At least three possible such mechanisms may exist: (1) use of one drug may alter brain substrates [persistently] in such a way that later use of another drug is more reinforcing, (2) withdrawal from one drug may trigger behavior to seek relief from those symptoms, including consumption of another drug, or (3) cues conditioned to the use of one drug may elicit cravings which can be satisfied by another drug. Using adolescent rats as subjects, we propose to attempt an animal model of adolescent drug progression, and to determine whether any of the above three alternatives may underlie such progression. Subjects will be preexposed to alcohol during the juvenile period, and later evaluated on three tests (schedule-induced polydipsia of cocaine solution, cumulative cocaine dosing effects on activity, and conditioned place preference) to determine if reactions to cocaine are altered in any of three conditions: during the acute withdrawal phase from alcohol, long after acute withdrawal is concluded, and in the presence of cues formerly associated with alcohol. The proposed work will be the first attempt to develop an animal model of drug progression, and may have implications for both understanding and treatment of adolescent substance abuse, as well as continuing to define the plasticity of the CNS during later development.

This project from George Mason University (Mason) creates an NSF I-Corps Site that will have a close affiliation with the Washington DC I-Corps Node.

NSF Innovation Corps (I-Corps) Sites are NSF-funded entities established at universities whose purpose is to nurture and support multiple, local teams to transition their technology concepts into the marketplace. Sites provide infrastructure, advice, resources, networking opportunities, training and modest funding to enable groups to transition their work into the marketplace or into becoming I-Corps Team applicants.
I-Corps Sites also strengthen innovation locally and regionally and contribute to the National Innovation Network of mentors, researchers, entrepreneurs and investors.

An NSF I-Corps Site at Mason will aid in the creation of a commercialization facilitation infrastructure that will enhance the impact of existing and future entrepreneurial training and support activities and will demonstrate the value of entrepreneurship education to the Mason community. The I-Corps Site will impact the preparedness of university talent for roles in technology-based entrepreneurial enterprises and as such will be a critical ingredient of the economic success of Virginia and the United States as a whole. With an I-Corps Site, Mason's commercialization facilitation activities will support a shift from an economy dependent on traditional employers to an entrepreneurially-driven economy. As more startups begin to flourish, new jobs will be created and the career prospects of future graduates will be strengthened. On the national level, there is valid concern that the US is losing its standing as the global leader in technology. Mason's activities will counter this trend by teaching university researchers to think beyond traditional academic boundaries, thus enabling this group of highly-talented scientists to become drivers of innovation within technology-based entrepreneurial companies that they help to create.