측핵 Dopamine계가 장소선호과제의 수행에 미치는 영향 = Effects of the Nucleus Accumbens Dopamine on the Place Preference Conditioning

국문 초록 (Abstract)

본 연구는 측핵의 dopamine성 입력이 먹이와 같은 자연적 강화자의 강화효과를 매개하는 신경화학적 실체인가를 규명하기 위하여 실험 1에서는 측핵의 dopamine성 신경종말을 6-OHDA로 손상시켰으며, 실험 2와 실험 3에서는 dopamine성 수용기를 차단하는 약물인 haloperidol을 측핵에 주입하였다. 그리고 행동적으로 강화의 효과를 평가하기 위하여 조건화된 장소선호를 측정하였다. 실험결과는 측핵의 dopamine성 신경종말이 파괴되거나 또는 측핵의 dopamine성 수용기가 차단되면 조건화된 장소선호에 결함이 나타나는 것으로 밝혀졌다. 그리고 이러한 실험처치들이 동물이 섭취한 먹이의 양이나 왕복상자에서의 이동회수에는 영향을 주지 않는 것으로 나타났다. 따라서 측핵의 dopamine성 입력이 차단된 동물에게서 나타난 조건화된 장소선호의 결함이 동기적인 요인이나 운동결함에 기인한 것이 아니라 강화자의 강화적 속성이 차단되었기 때문이라 해석할 수 있었다. 또한 실험 3의 haloperidol+haloperidol 집단에서도 조건화된 장소선호가 나타나지 않은 것으로 보아 본 연구의 결과가 상태의존적 학습 때문이 아니라고 할 수 있었다. 나아가 실험 3의 식염수+haloperidol 집단에서도 조건화된 장소선호가 나타나지 않았는데, 이는 측핵의 dopamine성 전도가 조건강화자의 강화효과를 매개하는데에도 중요한 역할을 한다고 볼 수 있다. 본 연구의 결과들을 종합하면 뇌 자기자극이나 보상적 약물들의 강화적 효과에 관한 기존의 연구결과들과 일치하는 것으로써, 측핵으로 들어오는 피개선조로 dopamine이 강화자의 강화적 속성을 매개하는 신경화학적 실체임을 시사하였다.

다국어 초록 (Multilingual Abstract)

The purpose of this study was to examine the role of dopaminergic input to the nucleus accumbens in the reinforcing effects of natural rewards using the place preference paradigm. In experiment 1, 22 male albino rats were randomly assigned to three groups. One group had received 6-hydroxydopamine(6-OHDA) lesions of the nucleus accumbens. The other two groups were used as sham operated or no food control group, 6-OHDA lesion group did not show the conditioned place preference and it was similar to no food control group. However, there was no difference among the three groups in the amount of food intake and number of crossing. Experiment 2 was conducted to see whether dopaminergic receptors in the nucleus accumbens were involved in the food reinforcing process. Haloperidol(0.5㎕, 1.0㎕) was injected just before being placed in the non-preferred compartment with food, and saline was injected just before being placed in the preferred compartment with no food. Only saline was injected to two control groups, one group was received food in the non-preferred compartment and the other group was received no food in either compartment. Results revealed that haloperidol groups and no food control group did not show the conditioned place preference. And there was also no difference among the four groups in the amount of food intake and number of crossing. Experiment 3 was conducted to test state dependent explanation of the result of experiment 2, and also to examine whether tegmentostriatal dopamine influences to the response with conditioned reinforcer even when primary reinforcer is not presented. Thirty rats were randomly assigned to two groups. Either saline or haloperidol(0.5㎕) was injected with into the nucleus accumbens during the conditioning phase. Before the test phase, each group was sub-divided into two. Either saline or haloperidol(0.5㎕) was injected again to sub-groups just before being tested. Results revealed that only those rats that were injected with saline during conditioning and test phase significantly changed their preference to the compartment associated with food. None of the other three groups(saline+saline, haloperidol+haloperidol, haloperidol+saline treated) changed their preference. These results indicated that the deficit in haloperidol treated rats was not due to the state dependent learning, and that haloperidol blocked the response to the conditioned reinforcer. Taken together it may be concluded that tegmentostriatal dopamine takes part in the reinforcement process of natural reward.

목차 (Table of Contents)

• 실험 1
• 방법
• 결과
• 실험 2
• 방법
• 결과
• 실험 3
• 방법
• 결과
• 논의
• 참고문헌