CIRCADIAN PATTERNS OF BEHAVIOR AND GENE EXPRESSION FOLLOWING ?RECREATIONAL? OR ?

University Of Louisville, Louisville KY

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal of the research is to compare behavioral and gene expression changes produced by a "recreational" pattern of drug use and by a pattern entailing abuse. Our subjects are rats. For the behavioral work, each animal will be continuously housed in a station with a 12-12 hour light-dark cycle and devices for providing food and water. Food intake will be monitored 24 hours a day. One group of animals will be exposed to a regime that mimics recreational drug use: They will receive a moderately high but non-toxic dose of amphetamine (2.0 mg/kg) at five-day intervals. A transient withdrawal state or "hangover," characterized by hypo-activity and reduced food intake occurs 18-26 hours after this dose. Another group of animals will be exposed to an escalating "binge" pattern of amphetamine administration. After food intake stabilizes, five-day tests will be run. On test day 1, animals will receive a saline administration, and on day 3 they will receive a "challenge" administration of 2.0 mg/kg amphetamine. Circadian patterns of food intake produced by the binge regime will be compared to those produced by a recreational drug use regime. For the gene expression work, rats will be housed in individual tubs in cabinets, and they will receive recreational or binge amphetamine and tests according to the schedule just described for the behavioral studies. We will assess expression for genes related to dopamine, glutamate and GABA receptors, in nucleus accumbens, dorsal striatum, and frontal cortex, at times corresponding to the psychomotor stimulant state (hour 1-6 post-treatment) and the transient withdrawal state observed during the recreational drug use regime. INBRE provided funding to support an individual who will conduct this research. So far the individual has received training on some of the behavioral and pharmacological procedures that will be employed in the study.