title: Behavioral and transcriptional patterns of protracted opioid self-administration in mice.
abstract: Chronic exposure to opioids induces adaptations in brain function that lead to the formation of the behavioral and physiological symptoms of drug dependence and addiction. Animal models commonly used to test these symptoms typically last less than two weeks, which is presumably too short to observe the alterations in the brain that accompany drug addiction. Here, we analyzed the phenotypic and molecular effects of nearly lifelong morphine or saccharin intake in C57BL/6J mice. We used multiple paradigms to evaluate the symptoms of compulsive drug intake: a progressive ratio schedule, intermittent access and a schedule involving a risk of punishment were programmed into an automated IntelliCage system. Gene expression profiles were evaluated in the striatum using whole-genome microarrays and further validated using quantitative polymerase chain reaction in the striatum and the prefrontal cortex. Mice voluntary self-administering morphine showed addiction-related behavioral pattern that included: higher motivation to work for a drug reward, increased reward seeking and increased craving. The analysis of molecular changes revealed a tolerance effect in the transcriptional response to morphine injection (20 mg/kg, ip), as well as some long-lasting alterations in gene expression profiles between the analyzed groups of animals. Interestingly, among the morphine-drinking animals, certain transcriptional profiles were found to be associated with alterations in behavior. In conclusion, our model represents a novel approach for investigating the behavioral and molecular mechanisms underlying opioid addiction. Prolonged morphine intake caused adaptive processes in the brain that manifested as altered behavior and transcriptional sensitivity to opioids.
authors: Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Poland.
authors: Urszula
authors: U
authors: Skupio
authors: Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Poland.
authors: Magdalena
authors: M
authors: Sikora
authors: Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Poland.
authors: Michal
authors: M
authors: Korostynski
authors: Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Poland.
authors: Agnieszka
authors: A
authors: Wawrzczak-Bargiela
authors: Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Poland.
authors: Marcin
authors: M
authors: Piechota
authors: Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Poland.
authors: Joanna
authors: J
authors: Ficek
authors: Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Poland.
authors: Ryszard
authors: R
authors: Przewlocki
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D053263:Gene Regulatory Networks / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009293:Opioid-Related Disorders / Q000503:physiopathology*; D012646:Self Administration
chemical_list: D000701:Analgesics, Opioid
keywords: addiction; gene expression; model; opioid; reward