量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果（学会誌発表論文、学会発表、研究開発報告書、特許等）を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum and Radiological Science and Technology.
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Drug addiction is characterized by psychic dependence, namely constant uncontrollable craving for drugs. This state may result from an aberrant memory of the drug-induced feeling, acompanied with the brain plasticity, such as long-term potentiation (LTP), that play a crucial role for learning and memory. Also, the development may be caused by the increase in extracellular dopamine concentration induced by the exposure to the addicitive drugs. It is well known that as an animal model, drug addicition (psychic dependence) can be represented by intravenous self-adminstration of drug, especially with progressive ratio (PR) schedule of reinforcement, in which the number of lever presses required on each consecutive run increase by a fixed gain. However, there is so far no distinctive literature showing in vivo neural substrates underlying the psychic dependence on drugs. Now, we aim to explore in vivo functional substrates underlying the psychic dependence on cocaine by measuring regional cerebral blood flow (rCBF) when macaques were performing intravanous self-administration of cocaine on PR schedule using positron emssion tomography (PET) with O-15 labeled water. In this study, when a LED was turned on as a visual cue for the initiation of the task, two rhesus monkeys (males, weighting 5-7 kg) were required to press a lever on a PR (1.2 increment ratio) schedule of reinforcement (cocaine or food). Before the PET scan session, we measured reinforcement strenghth of both cocaine and food reinforcement as stable breaking points of their lever-pressing behaviors. Our PET results showed the increases of rCBF in dorsolateral prefrontal cortex (PFC), orbitoforntal cortex, anterior cingulate cortex, nucleus accumbens (NAc), striatum, thalamus, and ventral tegmental area (VTA) in cocaine reinforcement condition, relative to food (banana-flavored pellet) reinforcement condition as control. These findings are consistent with the reports from a series of in vitro studies showing the plasticity, starting with LTP in VTA, NAc to PFC. Therefore, PET measurement may be very useful for demonstrating in vivo functional organization responsible for drug addiction.
PET investigation of monkey brain activation during intravenous cocaine self-administration
