Operant Responding in Opioid-Deficient Mice

Oregon Health And Science University, Portland OR

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Abstract

DESCRIPTION (provided by applicant): A widely held view of the mechanism underlying the reinforcing properties of opiates, thereby contributing to drug craving, is that drugs such as morphine and heroin usurp existing neural circuits that mediate the incentive value of natural reinforcers. If this is true, then one would expect that positive stimuli may be identical at the motivational level while differing at the perceptual or discriminative level. Pharmacology has suggested this to be the case, in that endogenous opioids modulate neural circuits involved in motivation to differing classes of stimuli, namely food and drugs of abuse. There remain many questions concerning the function of specific endogenous opioid peptides in the modulation of reward to positive stimuli. Our laboratory and others have generated mutant mice lacking specific opioid peptides or receptors to characterize the physiological function of these molecules. The proposed experiments are designed to test our hypothesis that the endogenous opioid peptides fulfill specific functions in modulating the incentive value of different classes of positive stimuli. The animal models we will use are fully congenic strains of C57BL/6J and DBA/2J mice harboring single mutations that result in the total absence of either Beta-endorphin, all forms of enkephalin, or a combination of both opioid peptide families. The primary behavioral task to assess reward is operant responding for food, saccharin, or morphine. Since the incentive value of positive stimuli vary with motivational states, we will study operant responding in the mice under both deprived and non-deprived conditions. Additional behavioral tasks that will be assessed in all groups of mice to further test the specificity of differences in operant responding include response extinction, measurements of taste preference, and locomotor activity.