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Show 209 THE UNIVERSITY OF UTAH Methamphetamine (METH) is a central nervous system (CNS) stimulant drug that increases the release and blocks the reuptake of the neurotransmitter dopamine (DA). As a result, excess DA accumulates in the brain providing a "rush" for persons who abuse this drug. DA is involved with the mechanisms of reward, motivation, pleasure and motor function. These desirable affects give METH a high potential for abuse. Neurotensin (NT) is a neuropeptide with neurotransmitter and modulatory activity in the CNS. NT also has been implicated in the pathophysiology of stimulants of abuse. In previous research we indicated that high doses of METH induced increases in neurotensin-like immunoreactivity (NTLI) tissue content in limbic and extrapyramidal systems. The present study was designed to determine the response of limbic NT pathways to varying low doses of METH. Sprague-Dawley rats received multiple administrations of various low doses of METH (0.2, 0.5 and 1.0 mg/kg, s.c.; 4 injections at 2-h intervals), and were sacrificed 5 h after drug treatment. Results revealed that this METH treat-ment significantly decreased NTLI concentration in anterior caudate (AC), posterior caudate (PC), and nucleus accumbens shell (NAs) limbic regions. These data demonstrate opposite responses of the limbic NT systems to low and high doses of METH and may suggest that a combination of dopamine D1 and D2 receptors activity surprisingly contribute to both effects. Additional studies are required to determine the functional implications of these peptide changes and identify the underlying mechanisms. Supported by NIDA grants DA13367 and DA00378 EFFECTS OF LOW DOSES OF METH ON LIMBIC NEUROTENSIN SYSTEMS Nathaniel M. Cordova (Mario E. Alburges, Glen R. Hanson) Department of Pharmacology and Toxicology University of Utah health sciences leap program Nathaniel M. Cordova Mario E. Alburges |