title: Micro-opioid receptor activation in the basolateral amygdala mediates the learning of increases but not decreases in the incentive value of a food reward.
abstract: The decision to perform, or not perform, actions known to lead to a rewarding outcome is strongly influenced by the current incentive value of the reward. Incentive value is largely determined by the affective experience derived during previous consumption of the reward-the process of incentive learning. We trained rats on a two-lever, seeking-taking chain paradigm for sucrose reward, in which responding on the initial seeking lever of the chain was demonstrably controlled by the incentive value of the reward. We found that infusion of the μ-opioid receptor antagonist, CTOP (d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH(2)), into the basolateral amygdala (BLA) during posttraining, noncontingent consumption of sucrose in a novel elevated-hunger state (a positive incentive learning opportunity) blocked the encoding of incentive value information normally used to increase subsequent sucrose-seeking responses. Similar treatment with δ [N, N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI 174,864)] or κ [5'-guanidinonaltrindole (GNTI)] antagonists was without effect. Interestingly, none of these drugs affected the ability of the rats to encode a decrease in incentive value resulting from experiencing the sucrose in a novel reduced-hunger state. However, the μ agonist, DAMGO ([d-Ala2, NMe-Phe4, Gly5-ol]-enkephalin), appeared to attenuate this negative incentive learning. These data suggest that upshifts and downshifts in endogenous opioid transmission in the BLA mediate the encoding of positive and negative shifts in incentive value, respectively, through actions at μ-opioid receptors, and provide insight into a mechanism through which opiates may elicit inappropriate desire resulting in their continued intake in the face of diminishing affective experience.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, California 90024, USA. kwassum@ucla.edu
authors.forename: Kate M
authors.initials: KM
authors.lastname: Wassum
authors.forename: Ingrid C
authors.initials: IC
authors.lastname: Cely
authors.forename: Bernard W
authors.initials: BW
authors.lastname: Balleine
authors.forename: Nigel T
authors.initials: NT
authors.lastname: Maidment
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D004328:Drive; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000008:administration & dosage / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D005502:Food; D006146:Guanidines; D008297:Male; D008845:Microinjections; D009019:Morphinans; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D009483:Neuropsychological Tests; D051381:Rats; D020318:Rats, Long-Evans; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000037:antagonists & inhibitors*; D012201:Reward; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D013395:Sucrose
chemical_list: C411465:17-cyclopropylmethyl-6,7-didehydro-4,5-epoxy-5'-guanidinyl-3,14-dihydroxyindolo(2',3'-6,7)morphinan; D006146:Guanidines; D009019:Morphinans; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D013004:Somatostatin; D013395:Sucrose; D004743:Enkephalin, Leucine; D009271:Naltrexone; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine