Nicotine is a psychomotor stimulant with ‘reinforcement enhancing’ effects — the actions of nicotine in the brain increase responding for non-nicotine rewards. We hypothesized that this latter effect of nicotine depends on increased incentive properties of anticipatory cues; consistent with this hypothesis, multiple laboratories have reported that nicotine increases sign tracking, i.e. approach to a conditioned stimulus (CS), in Pavlovian conditioned-approach tasks. Incentive motivation and sign tracking are mediated by mesolimbic dopamine (DA) transmission and nicotine facilitates mesolimbic DA release. Therefore, we hypothesized that the incentive-promoting effects of nicotine would be impaired by DA antagonists. To test this hypothesis, separate groups of rats were injected with nicotine (0.4 mg/kg base) or saline prior to Pavlovian conditioning sessions in which a CS (30 s illumination of a light or presentation of a lever) was immediately followed by a sweet reward delivered in an adjacent location. Both saline and nicotine pretreated rats exhibited similar levels of conditioned approach to the reward location (goal tracking), but nicotine pretreatment significantly increased approach to the CS (sign tracking), regardless of type (lever or light). The DAD1 antagonist SCH-23390 and the DAD2/3antagonist eticlopride reduced conditioned approach in all rats, but specifically reduced goal tracking in the saline pretreated rats and sign tracking in the nicotine pretreated rats. The non-selective DA antagonist flupenthixol reduced sign-tracking in nicotine rats at all doses tested; however, only the highest dose of flupenthixol reduced goal tracking in both nicotine and saline groups. The reductions in conditioned approach behavior, especially those by SCH-23390, were dissociated from simple motor suppressant effects of the antagonists. These experiments are the first to investigate the effects of dopaminergic drugs on the facilitation of sign-tracking engendered by nicotine and they implicate dopaminergic systems both in conditioned approach as well as the incentive-promoting effects of nicotine.

過去有關壓力的研究指出，當對實驗動物施予單次禁錮、足部或尾部電擊或是實驗者的抓取動作等壓力源時，其大腦中的前額葉皮質、杏仁核、依核或是紋狀體等處會有隨壓力源產生的多巴胺分泌量增加現象。相對於壓力源對腦中神經化學物質的探討，壓力源對與學習制約有關的行為影響的相關研究證據迄今如缺，因此本研究企圖建立單次壓力源操弄對場地制約偏好行為的動物模式。實驗一A對大白鼠施予單次30分鐘的高台壓力源，發現確實可建立場地制約偏好行為。實驗一B操弄單次高台壓力源觀察其對實驗動物自發性活動量的影響，結果發現其對於實驗受試在大動作持續時問上具有抑制效果。實驗一C操弄單次高台壓力源後的0、30、60及120分鐘時採取實驗受試的前額葉皮質、海馬體、杏仁核、依核及紋狀體等五處組織，檢驗其多巴胺、血清張力素及代謝物的含量。結果發現除海馬體外的四個部位的多巴胺量及其代謝物分別在不同採集時間點有不等的顯著增加現象。血清張力素的變化量在各個部位不及多巴胺。實驗二及實驗三分別經由周邊或中樞前額葉皮質微量注射多巴胺D₁與D₂專屬受體拮抗劑，結果發現其可抑制曲單次高台壓力源操弄所建立的場地制約偏好行為。綜合上述結果，單次高台壓力源的操弄確實可引發大白鼠大腦中的多巴胺量增加藉以形成場地制約偏好行為，而此場地制約偏好行為所依賴的多巴腰量增加位置推論其是依核而非前額葉皮質。另外，多巴胺D1與D2受體對此高台壓力源引發的場地制約偏好行為所扮演的角色相當。 / When experimental animals under single stressor, such as restraint, foot, or tail-shock, or handing, an immediate and robust releasing of dopamine appears in the prefrontal cortex, amygdala, nucleus accumbens, or striatum. In contrast to these neurochemical findings, the behavioral effects under stress are rarely studied and remained uncertain. The purpose of this study was to establish an animal model of single stress-induced conditioned place preference (CPP). Experiment 1A found that the CPP can be induced by a single high-plate stressor. Experiment 1B investigated the effects of this single high plate stressor on rats' locomotion, this stressor was found to inhibit the large movement as measured by duration. Experiment 1C investigated the timing course of this stressor on dopamine, serotonin, and their metabolities in the prefrontal cortex, hippocampus, amygdala, nucleus accumbens, and striatum. The results showed that all the areas, except hippocampus, had distinct patterns of changes on dopamine, serotonin and their metabolities at different times' after stress. Experiment 2 and 3, examined the effects ofdopamine D1 or D2 receptor antagonists, administered respectively via intraperitoneal or local infusion into the prefrontal cortex, on the CPP formed after high-plate stress. The results showed that these drug manipulations can inhibit stress-induced CPP. Taken together, these results indicated the CPP formed after high-plate stressor is developed on the immediate increase ofdopamine releases in the nucleus accumbens and prefrontal cortex. These neurochemical alterations are more profound in the nucleus accumbens than the prefrontal cortex. However, the dopamine D₁ and D₂ receptor in the prefrontal cortex are also important for the formation of CPP after high-plate stressor.