Behavioral and transcriptional patterns of protracted opioid self-administration in mice
Addiction Biology. 2016-08-31; 22(6): 1802-1816
DOI: 10.1111/adb.12449
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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.
© 2016 Society for the Study of Addiction.