A Novel Morphine Drinking Model of Opioid Dependence in Rats. 2022

Pablo Berríos-Cárcamo, and Mauricio Quezada, and Daniela Santapau, and Paola Morales, and Belén Olivares, and Carolina Ponce, and Alba Ávila, and Cristian De Gregorio, and Marcelo Ezquer, and María Elena Quintanilla, and Mario Herrera-Marschitz, and Yedy Israel, and Fernando Ezquer
Center for Regenerative Medicine, Faculty of Medicine Clínica Alemana, Universidad del Desarrollo, Santiago 7610658, Chile.

An animal model of voluntary oral morphine consumption would allow for a pre-clinical evaluation of new treatments aimed at reducing opioid intake in humans. However, the main limitation of oral morphine consumption in rodents is its bitter taste, which is strongly aversive. Taste aversion is often overcome by the use of adulterants, such as sweeteners, to conceal morphine taste or bitterants in the alternative bottle to equalize aversion. However, the adulterants' presence is the cause for consumption choice and, upon removal, the preference for morphine is not preserved. Thus, current animal models are not suitable to study treatments aimed at reducing consumption elicited by morphine itself. Since taste preference is a learned behavior, just-weaned rats were trained to accept a bitter taste, adding the bitterant quinine to their drinking water for one week. The latter was followed by allowing the choice of quinine or morphine (0.15 mg/mL) solutions for two weeks. Then, quinine was removed, and the preference for morphine against water was evaluated. Using this paradigm, we show that rats highly preferred the consumption of morphine over water, reaching a voluntary morphine intake of 15 mg/kg/day. Morphine consumption led to significant analgesia and hyperlocomotion, and to a marked deprivation syndrome following the administration of the opioid antagonist naloxone. Voluntary morphine consumption was also shown to generate brain oxidative stress and neuroinflammation, signs associated with opioid dependence development. We present a robust two-bottle choice animal model of oral morphine self-administration for the evaluation of therapeutic interventions for the treatment of morphine dependence.

UI MeSH Term Description Entries
D009020 Morphine The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. Morphine Sulfate,Duramorph,MS Contin,Morphia,Morphine Chloride,Morphine Sulfate (2:1), Anhydrous,Morphine Sulfate (2:1), Pentahydrate,Oramorph SR,SDZ 202-250,SDZ202-250,Chloride, Morphine,Contin, MS,SDZ 202 250,SDZ 202250,SDZ202 250,SDZ202250,Sulfate, Morphine
D009021 Morphine Dependence Strong dependence, both physiological and emotional, upon morphine. Morphine Abuse,Morphine Addiction,Abuse, Morphine,Addiction, Morphine,Dependence, Morphine
D009293 Opioid-Related Disorders Disorders related to or resulting from abuse or misuse of OPIOIDS. Opiate Addiction,Opiate Dependence,Opioid Misuse,Opioid Use Disorder,Prescription Opioid Abuse,Prescription Opioid Misuse,Addiction, Opioid,Dependence, Opioid,Opiate Abuse,Opioid Abuse,Opioid Addiction,Opioid Dependence,Abuse, Opiate,Abuse, Opioid,Abuse, Prescription Opioid,Addiction, Opiate,Dependence, Opiate,Disorder, Opioid Use,Misuse, Opioid,Misuse, Prescription Opioid,Opiate Abuses,Opioid Abuse, Prescription,Opioid Abuses,Opioid Addictions,Opioid Dependences,Opioid Misuses,Opioid Related Disorders,Opioid Use Disorders,Opioid-Related Disorder,Prescription Opioid Abuses,Prescription Opioid Misuses
D011803 Quinine An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. Biquinate,Legatrim,Myoquin,Quinamm,Quinbisan,Quinbisul,Quindan,Quinimax,Quinine Bisulfate,Quinine Hydrochloride,Quinine Lafran,Quinine Sulfate,Quinine Sulphate,Quinine-Odan,Quinoctal,Quinson,Quinsul,Strema,Surquina,Bisulfate, Quinine,Hydrochloride, Quinine,Sulfate, Quinine,Sulphate, Quinine
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013649 Taste The ability to detect chemicals through gustatory receptors in the mouth, including those on the TONGUE; the PALATE; the PHARYNX; and the EPIGLOTTIS. Gustation,Taste Sense,Gustations,Sense, Taste,Senses, Taste,Taste Senses,Tastes
D014867 Water A clear, odorless, tasteless liquid that is essential for most animal and plant life and is an excellent solvent for many substances. The chemical formula is hydrogen oxide (H2O). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Hydrogen Oxide
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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