The Speed of Intravenous Cocaine Delivery Alters its Effect on the Brain and Drug-Taking Behavior: Implications for Addiction Liability.

Self-administration;Extended Access;Immediate Early Gene;Reinstatement;Nucleus Accumbens;Route of Administration;Neurosciences;Health Sciences;Neuroscience

Wakabayashi, Ken TaroSarter, Martin Friedrich ;

University of Michigan

关键词: Self-administration;    Extended Access;    Immediate Early Gene;    Reinstatement;    Nucleus Accumbens;    Route of Administration;    Neurosciences;    Health Sciences;    Neuroscience;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/75876/ktwakaba_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Cocaine addiction in humans is a severe health and social problem. Therefore, understanding how casual use transforms into addiction is critical. One of the many factors that can facilitate addiction is how rapidly drugs like cocaine enter the brain. Faster rates of cocaine delivery have a greater neurobiological impact on brain reward systems, producing sensitization. This may facilitate the transition to addiction by changing systems in the brain underlying reward. Yet most studies in the rat have shown few effects of rate of delivery on drug-taking behavior. Recently, paradigms have been developed where rats given extended access to take cocaine develop addiction-like behaviors. If the rate of drug delivery influences its addictive liability, it can be predicted that faster rates of cocaine delivery will be associated with a greater neurobiological impact and addiction-like behavior. The studies in this dissertation tested this prediction. In the first study, fast rates (5 sec) of infusion induced more Fos expression, a marker for neurobiological impact, than slower rates (25 – 100 sec). This effect was equally evident in the patch and matrix subcompartments of the striatum, a brain reward sub-system implicated in addiction, suggesting that fast rates of infusion had a widespread impact on this structure. In the second study, faster rates (5 – 45 sec) of cocaine infusion facilitated an escalation in overall drug intake in contrast to slower rates (90 sec) when rats were given extended, but not limited, access to cocaine. In the third study, fast (5 sec) rates of cocaine infusion during extended access self- administration was associated with a persistence to reinstate drug-seeking behavior in response to a drug induced priming injection 45 days after their last self-administration session. This behavior in the 5 sec group was also associated with more persistent neuroadaptations in the brain. Thus, faster rates of cocaine infusion have a greater and more persistent impact on brain reward systems, and facilitate the development of behaviors that resemble addiction. This may be one reason why routes of administration that result in the rapid entry of cocaine into the brain, may preferentially promote the transition to addiction.