Pathological Gambling (PG) is an impulse control disorder with lifetime prevalence of 1-3%. Available treatments are limited by uncertain classification and complexity of implicated neurotransmitter systems. Dopamine (DA), a key neurotransmitter implicated in addictive behavior and reward is elevated in response to gambling and psychostimulants. Based on previous research, it was hypothesized that the D2 blocker, haloperidol (HAL), will enhance slot machine reinforcement in PG but not in Healthy Controls (HC). If this increase reflects preferential stimulation of D1 receptors and group differences in D1 sensitivity, D1-D2 blocker (fluphenazine, FLU) should offset increase in reinforcement seen with HAL in PG subjects. In line with DA's implicated role in 'wanting' vs. 'liking' of the addictive reinforcer, the results suggest that DA release mediated partial D1 activation under FLU led to clear differentiation between groups with increased 'wanting' seen in controls but not in gamblers. DA's role in 'liking' however remains elusive.

Pathological Gambling (PG) is an impulse control disorder with lifetime prevalence of 1-3%. Available treatments are limited by uncertain classification and complexity of implicated neurotransmitter systems. Dopamine (DA), a key neurotransmitter implicated in addictive behavior and reward is elevated in response to gambling and psychostimulants. Based on previous research, it was hypothesized that the D2 blocker, haloperidol (HAL), will enhance slot machine reinforcement in PG but not in Healthy Controls (HC). If this increase reflects preferential stimulation of D1 receptors and group differences in D1 sensitivity, D1-D2 blocker (fluphenazine, FLU) should offset increase in reinforcement seen with HAL in PG subjects. In line with DA's implicated role in 'wanting' vs. 'liking' of the addictive reinforcer, the results suggest that DA release mediated partial D1 activation under FLU led to clear differentiation between groups with increased 'wanting' seen in controls but not in gamblers. DA's role in 'liking' however remains elusive.

The role of endogenous dopamine, utilizing a dopamine antagonist (fluphenazine; FLU), in modulation of gonadotropin, growth hormone (GH) and prolactin (PRL) secretion during the early postpartum period and various stages of the estrous cycle was investigated in Holstein cows. Experiment 1 was conducted in anovulatory early postpartum cows. Fluphenazine caused a decrease (P < .05) in mean serum LH concentration and LH pulse frequency. Likewise, FLU caused a (P < .05) decrease in mean GH concentration. These results suggest that endogenous dopamine, at least in part, is responsible for regulation of LH and GH secretion in anovulatory Holstein cows. Experiment 2 was conducted in cyclic lactating Holstein cows during the mid-luteal phase of the estrous cycle. Mean serum LH and FSH concentrations, pulse frequencies, and peak amplitudes did not change in response to FLU. FLU did not affect mean serum GH concentration. These results suggest that a dopamine-mediated mechanism for modulation of gonadotropin and GH secretion is absent or perhaps overridden by high progesterone concentration during the luteal phase of the estrous cycle in lactating dairy cows. Experiment 3 was conducted during the early follicular phase of the estrous cycle in Holstein cows. During the follicular phase, FLU caused a decrease (P < .05) in mean serum LH concentration and LH pulse frequency. However, FLU had no effect on mean serum FSH concentration or pulse frequency. Further, FLU increased (P < .05) GH concentrations during the follicular phase. Experiment 4 was conducted during the early metestrus phase of the estrous cycle. During the metestrus phase, FLU tended to decrease (P < .1) mean LH concentration and suppressed (P < .05) LH pulse frequency but had no effect on FSH secretion. Fluphenazine caused a transient increase (P < .05) in mean serum GH concentration. The results of the third and fourth experiments suggest that, during the early follicular and metestrus phases of the estrous cycle, when progesterone concentration is low, modulation of LH and GH secretion, at least in part, is modulated by endogenous dopamine. However, a dopamine mediated mechanism for FSH secretion is absent during both phases of the estrous cycle in lactating Holstein cows. In all experiments FLU increased (P < .01) PRL secretion indicating that endogenous dopamine suppresses PRL secretion in cattle regardless of ovarian status. It is concluded that: 1) endogenous dopamine plays a stimulatory role in LH secretion during the anovulatory postpartum period and during the estrous cycle only when serum progesterone is low. 2) FLU decreased GH secretion in anovulatory postpartum Holstein cows but it increased GH secretion during the follicular and metestrus phases of the estrous cycle. However FLU had no effect on GH secretion during the luteal phase of the estrous cycle. Thus it appears that, modulation of GH secretion is dependent upon reproductive status and ovarian hormones secretion. / Ph. D.

本研究探討舔飲蔗糖液之成本利益情境中，多巴胺受體拮抗劑對舔飲行為配置的影響，以釐清阻斷多巴胺使行為受損的條件與所代表之意義。實驗設計為「高位置高濃度糖液＋低位置低濃度糖液」雙管情境中的舔飲行為，實驗一確立高、低位置分別代表高、低成本後，實驗二至實驗七調整糖液濃度、裝盛容器與舔飲經驗，發現唯有「高位置籠外水管20％糖液＋低位置伸入式水瓶15％糖液」且增加單獨對低瓶的舔飲經驗，方能建立多巴胺受體拮抗劑的「此降彼升」動物模式。實驗八確認「此降彼升」的三要件為低位置是（1）低成本：伸入式容器、（2）高利益：15％糖液、（3）充足經驗：9天舔飲低瓶。實驗九至十一的藥物測試得到前述動物模式可有效區別多巴胺受體拮抗劑、降低食量藥物與干擾動作藥物有不同影響型態。實驗十二發現單管情境與雙管情境的結果有很高的一致性。結論為（1）較低劑量的多巴胺受體拮抗劑並不減少大白鼠對糖液的總需求、不干擾兩者行為間的區辨選擇與轉換能力，（2）舔飲行為不受多巴胺受體拮抗劑干擾的要件為低成本、高利益與充足經驗三者需同時成立，（3）不符三要件之舔飲行為會因多巴胺受體拮抗劑而降低表現量，因此反駁過去認為完結行為不受此類藥物干擾的想法，（4）本研究建立的雙管舔飲情境可有效區分不同藥物作用，值得做為進一步探討多巴胺與行為之間的關係及其神經機制的動物模式。 / This study investigated the effect of dopamine antagonist on licking sucrose solution behavior under cost-benefit condition, which was designed into a 'high-cost high-benefit with low-cost low-benefit' licking test situation. Experiment 1 confirmed that the difference of licking response between high and low positions indicating the cost difference. Experiment 2 to Experiment 7, manipulating the liquid container, sucrose concentration and the experience of licking low position solution, found that rats only increased low position sucrose intake while decreased high position one in 'high tube 20% with low bottle 15% sucrose solution' condition. Experiment 8 further confirmed three factors of low cost, high benefit and plenty experience were necessary for increasing intake of low position in simultaneous contrast to decreasing the intake of high position. Experiment 9 to Experiment 11 evaluated the drug effects of dopamine antagonists, anorectics and motor relaxants on the present animal model. The results showed the different patterns of reaction for these three types of drugs. Experiment 12 revealed the results of single tube condition were consistent with those of cost-benefit condition. Together, these results demonstrated that dopamine antagonist neither decrease the drive for sucrose nor disrupt the abilities to discriminate and select between two tubes under the present model. Three factors of cost, benefit and experience are important to determine dopamine antagonist effect. Therefore, the resistance of consummatory behavior to dopamine dysfunction may be limited for specific situation. And, the cost-benefit licking model can be useful for further investigation of neurobehavioral mechanism of dopamine system.