抑制外側韁核對大鼠場地制約的影響效果

Effects of inactivation of the lateral habenula on place conditioning in rats

楊季樺(Yang Chi-Hua)

指導教授 ： 廖瑞銘 ； 趙知章

國立政治大學/理學院/神經科學研究所/碩士(2018年)

https://doi.org/10.6814/THE.NCCU.IN.001.2018.C05

摘要

個體面對不同的外部刺激選擇合宜的行為反應，同時對環境的變化具備行為調整與學習之能力有助於生物體的存活。中腦邊緣多巴胺系統在上述行為中扮演重要的角色，其涉及個體的酬賞動機與聯結學習等認知行為。根據神經解剖學與行為神經科學的研究，外側韁核可以調控中腦邊緣多巴胺系統進而影響酬賞相關的動機行為；迄今絕大多數研究是使用操作式制約行為作業檢測外側韁核的神經活動與酬賞相關行為的關係，較少研究探討抑制外側韁核對於多巴胺相關之古典式制約行為的影響。因此本研究透過藥理抑制的方式，探討外側韁核的GABA受體對於場地制約行為的影響。實驗一的結果顯示GABAa受體致效劑muscimol注入外側韁核無法引發場地制約偏好(CPP)。實驗二的結果同時將muscimol及GABAb受體致效劑baclofen混合液(B/M)注入外側韁核無法形成CPP，惟有增加藥物制約配對箱的自發性活動量。實驗三進行周邊注射安非它命(d-AMP)0.5, 1, 2 mg/kg的劑量反應，發現其無法令受試習得CPP，但有增加藥物配對箱的行為活動量。實驗四進行B/M注入外側韁核結合腹腔注射d-AMP，其可有效地使受試習得CPP。綜合上述的實驗結果顯示，單獨以GABA類受體致效劑抑制外側韁核或以較低劑量的d-AMP周邊注射，皆無法讓個體形成顯著的CPP，而須在這兩項藥物處置同時進行方得顯著的CPP，這意含抑制外側韁核可以增強個體對於藥物酬賞相關的古典式制約學習行為。

關鍵字

場地制約偏好 ； 疆核 ； GABA受體致效劑 ； 心理興奮劑

並列摘要

The ability of appropriate reaction to different kinds of external stimuli as well as behavioral flexibility in cases of response reinforcement contingencies being changed are essential for survival. Such behaviors involved in reward motivation and associative learning are known to be mediated by the mesolimbic dopamine (DA) systems. In terms of anatomy and behavioral neuroscience, the lateral habenula (LHb) has been suggested to modulate reward-related behaviors that are mediated by the mesolimbic DA systems. While there have been a number of studies using operant conditioning task to Investigate the role of the LHb in reward-related behavior, less work has attended on the role of the LHb in reward-related behavior as measured by the tasks based on classical conditioning theory. Therefore, in the present study, we investigated the effects of inactivation of the LHb by using GABA agonists on place conditioning task. The results of Experiment 1 show that intra-LHb infusion of muscimol, a GABAa agonist, did not produce any significant place conditioning. The results of Experiment 2 show that a mixture of the GABAb and GABAa agonists, baclofen and muscimol (B/M), infused into the LHb did not establish any significant place conditioning; even with the enhanced locomotor activity observed in drug-paired chamber during the conditioning sessions. In Experiment 3, we examined the dose effects of d-amphetamine (d-AMP; 0, 0.5, 1, or 2 mg/kg; IP) on place conditioning, and there was no drug-induced conditioned place preference (CPP). Locomotor activity was enhanced by d-AMP in drug-paired chamber during the conditioning session. The results of Experiment 4 show that intra-LHb infusion of B/M combined with IP injection of d-AMP significantly induced CPP. These data demonstrated that neither intra-LHb infusion of GABA agonists alone nor systemic injection of d-AMP alone produced significant place conditioning, but a CPP was developed by two aforementioned drug treatments administered in combination. Thus, the inactivation of the LHb is indicated to facilitate the individual in acquiring task involved classical conditioning of drug reward to contextual cue.

並列關鍵字

Conditioned place preference ； Habenula ； GABA receptor agonist ； Psychostimulant

參考文獻

Akirav I, Raizel H, Maroun M (2006) Enhancement of conditioned fear extinction by infusion of the GABA(A) agonist muscimol into the rat prefrontal cortex and amygdala. Eur J Neurosci 23:758-764.

Baker PM, Jhou T, Li B, Matsumoto M, Mizumori SJY, Stephenson-Jones M, Vicentic A (2016) The lateral habenula circuitry: reward processing and cognitive control. J Neurosci 36:11482-11488.

Baker PM, Raynor SA, Francis NT, Mizumori SJY (2017) Lateral habenula integration of proactive and retroactive information mediates behavioral flexibility. Neuroscience 345:89-98.

Bardo MT, Valone JM, Bevins RA (1999) Locomotion and conditioned place preference produced by acute intravenous amphetamine: role of dopamine receptors and individual differences in amphetamine self-administration. Psychopharmacology 143:39-46.

Bressel PJRD, McNally GP (2014) The role of the lateral habenula in punishment. PLoS One 9:e111699.