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The Journal of Neuroscience, September 15, 2002, 22(18):8251-8258

Selective Reward Deficit in Mice Lacking -Endorphin and Enkephalin

Michael D. Hayward¹, John E. Pintar³, and Malcolm J. Low^{1, 2}

¹ The Vollum Institute and ² Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, Oregon 97201, and ³ Robert Wood Johnson Medical School, Department of Neuroscience and Cell Biology, Piscataway, New Jersey 08854

It has been impossible to unequivocally identify which endogenous opioids modulate the incentive value of rewarding stimuli because these peptides are not highly selective for any single opioid receptor subtype. Here, we present evidence based on the measurement of instrumental behavior of -endorphin and enkephalin knock-out mice that both opioid peptides play a positive role. A progressive ratio schedule was used to measure how hard an animal would work for food reinforcers. The loss of either opioid reduced responding under this schedule, regardless of the palatability of the three different formulas of reinforcers used. The phenotype of mice lacking both endogenous opioids was nearly identical to the phenotype of mice mutant for either individual opioid. Responses were tested in nondeprived and deprived feeding states but were reduced in -endorphin- and enkephalin-deficient mice only when they were maintained under nondeprived conditions. Other operant manipulations ruled out variables that might contribute nonspecifically to this result such as differences in acquisition, early satiation, motor performance deficit, and reduced resistance to extinction. In contrast to the effects on instrumental performance, the loss of either or both endogenous opioids did not influence preference for water flavored with sucrose or saccharin in a two-bottle free-choice drinking paradigm. We conclude that both -endorphin and enkephalin positively contribute to the incentive-motivation to acquire food reinforcers. Because the attenuation of operant responding was observed only during a nondeprived motivational state, the hedonics of feeding are likely altered rather than energy homeostasis.

Key words: endogenous opioids; reinforcement; operant conditioning; mouse; feeding; motivation

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22188251-08$05.00/0

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