Deletion of the δ Opioid Receptor Gene Impairs Place Conditioning But Preserves Morphine Reinforcement

• Published in: Biological psychiatry (1969) Vol. 69; no. 7; pp. 700 - 703
• Main Authors: Le Merrer, Julie, Plaza-Zabala, Ainhoa, Del Boca, Carolina, Matifas, Audrey, Maldonado, Rafael, Kieffer, Brigitte L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2011; Elsevier
• Subjects: Analgesics, Opioid - administration & dosage; Animals; Appetitive Behavior - drug effects; Behavior, Animal; Conditioning, Operant - drug effects; Conditioning, Operant - physiology; Discrimination (Psychology) - drug effects; Dose-Response Relationship, Drug; Escape Reaction - drug effects; Instrumental conditioning; knockout mice; Learning Disorders - genetics; Learning Disorders - physiopathology; Life Sciences; lithium; Mice; Mice, Knockout; Morphine - administration & dosage; motivation; Motivation - drug effects; opiate; Other; Psychiatry; Receptors, Opioid, delta - deficiency; Reinforcement (Psychology); reward; Self Administration; Space Perception - drug effects; Time Factors; reward; lithium; Instrumental conditioning; knockout mice; motivation; opiate
• ISSN: 0006-3223; 1873-2402; 1873-2402
• DOI: 10.1016/j.biopsych.2010.10.021

Converging experimental data indicate that δ opioid receptors contribute to mediate drug reinforcement processes. Whether their contribution reflects a role in the modulation of drug reward or an implication in conditioned learning, however, has not been explored. In the present study, we investigated the impact of δ receptor gene knockout on reinforced conditioned learning under several experimental paradigms. We assessed the ability of δ receptor knockout mice to form drug-context associations with either morphine (appetitive)- or lithium (aversive)-induced Pavlovian place conditioning. We also examined the efficiency of morphine to serve as a positive reinforcer in these mice and their motivation to gain drug injections, with operant intravenous self-administration under fixed and progressive ratio schedules and at two different doses. Mutant mice showed impaired place conditioning in both appetitive and aversive conditions, indicating disrupted context-drug association. In contrast, mutant animals displayed intact acquisition of morphine self-administration and reached breaking-points comparable to control subjects. Thus, reinforcing effects of morphine and motivation to obtain the drug were maintained. Collectively, the data suggest that δ receptor activity is not involved in morphine reinforcement but facilitates place conditioning. This study reveals a novel aspect of δ opioid receptor function in addiction-related behaviors.