Department of Psychiatry and Clinical Research Centre, Karolinska Institute, S-141 86 Huddinge, Sweden.
J Neuroendocrinol. 1992 Dec;4(6):727-34. doi: 10.1111/j.1365-2826.1992.tb00224.x.
The involvement of dopamine receptors in the inhibitory effect of Cholecystokinin octapeptide on ingestive behaviour was investigated. Male rats were infused intraorally with a 1 M solution of sucrose and the amount ingested after treatment with the dopamine receptor agonist apomorphine was compared with that after treatment with Cholecystokinin octapeptide. The test allows a distinction between the consummatory aspects of ingestive behaviour, i.e. responses used to ingest food, from the appetitive aspects, i.e. responses used to obtain food, because it ignores the latter aspects. Comparisons were also made between the effects of apomorphine and Cholecystokinin octapeptide on pellet intake, a test in which the rat has to display appetitive ingestive behaviour. Injection of apomorphine (400 μg) increased the concentration of plasma apomorphine within 0.3 min and the concentration of dopamine in the cerebrospinal fluid within 1 min of injection and induced behavioural stereotypes within 10 min in food-deprived male rats. Plasma apomorphine and cerebrospinal fluid dopamine levels had decreased by 30 min and the behavioural stereotypies had decreased by 40 min after the injection. Injection of apomorphine also inhibited the consumption of food pellets and the ingestion of sucrose. Inhibition of pellet and sucrose ingestion paralleled the effect of apomorphine on Stereotypie behaviour. Thus, injection of a dopamine receptor agonist is followed by alterations in plasma levels of the agonist, cerebrospinal fluid dopamine levels and in Stereotypie and ingestive behaviour which occur in parallel, in an inverted U-shaped manner and with a temporal delay between each event. These results show a close correlation between dopamine receptor stimulation and inhibition of ingestive behaviour. However, reversal of the inhibitory effect of apomorphine on ingestive behaviour required pretreatment with a lower dose of a dopamine receptor antagonist (cis-flupentixol) (0.1 mg) than reversal of Stereotypie behaviour (0.8 mg). The effect of dopamine receptor stimulation on consummatory ingestive behaviour is thus relatively weak and not secondary to the induction of Stereotypic behaviour. Treatment with a high dose of cis-flupentixol (0.8 mg) caused a prolonged period of immobility but had no effect on the ingestion of sucrose. Dopamine receptor blockade, therefore, interferes with appetitive, but not consummatory ingestive behaviour. Injection of Cholecystokinin octapeptide (5 μg) suppressed pellet and sucrose intake in a manner comparable to that of apomorphine, but induced no behavioural stereotypes and caused a gradual, rather than inverted U-shaped, increase in the concentration of dopamine in the cerebrospinal fluid that did not correlate with the effect on ingestive behaviour. Furthermore, while the inhibitory effect of apomorphine on the ingestion of sucrose was reversed by pretreatment with a low dose of cis-flupentixol (0.1 mg), the inhibitory effect of Cholecystokinin octapeptide was only partially reversed by cis-flupentixol and a higher dose (0.8 mg) was required. Blockade of cholecystokinin-A receptors, by treatment with L-364,718, but not cholecystokinin-B receptors, by treatment with L-365,260, blocked the inhibitory effect of Cholecystokinin octapeptide and, by itself, L-364,718 increased the amount of ingested sucrose. The inhibitory effect of Cholecystokinin octapeptide on consummatory ingestive behaviour, which is mediated by cholecystokinin-A receptors, is likely to involve mechanisms in addition to dopaminergic ones.
研究了多巴胺受体在胆囊收缩素八肽对摄食行为抑制作用中的参与情况。雄性大鼠经口腔内输注 1 M 蔗糖溶液，并比较了多巴胺受体激动剂阿朴吗啡处理后和胆囊收缩素八肽处理后摄入的量。该测试可区分摄食行为的消耗性方面，即用于摄入食物的反应，与食欲方面，即用于获得食物的反应，因为它忽略了后者方面。还比较了阿朴吗啡和胆囊收缩素八肽对丸剂摄入量的影响，丸剂摄入量是一种测试，其中大鼠必须表现出食欲性摄食行为。阿朴吗啡（400μg）的注射在 0.3 分钟内增加了血浆阿朴吗啡的浓度，并在注射后 1 分钟内增加了脑脊液中的多巴胺浓度，并在 10 分钟内诱导了饥饿雄性大鼠的行为刻板印象。注射后 30 分钟，血浆阿朴吗啡和脑脊液多巴胺水平下降，40 分钟后行为刻板印象下降。阿朴吗啡的注射也抑制了食物丸的消耗和蔗糖的摄入。丸剂和蔗糖摄入的抑制与阿朴吗啡对刻板行为的作用平行。因此，多巴胺受体激动剂的注射会导致激动剂的血浆水平、脑脊液多巴胺水平以及刻板和摄食行为的改变，这些改变以倒置的 U 形方式平行发生，并且每个事件之间存在时间延迟。这些结果表明，多巴胺受体刺激与摄食行为的抑制密切相关。然而，阿朴吗啡对摄食行为的抑制作用的逆转需要预先用较低剂量的多巴胺受体拮抗剂（顺式-氟哌丁醇）（0.1mg）治疗，而不是逆转刻板行为（0.8mg）。多巴胺受体刺激对摄食行为的消耗性作用因此相对较弱，并且不是刻板行为诱导的次要作用。用高剂量的顺式-氟哌丁醇（0.8mg）治疗会导致长时间的不动，但对蔗糖的摄入没有影响。因此，多巴胺受体阻断会干扰食欲，但不会干扰摄食行为。胆囊收缩素八肽（5μg）的注射以类似于阿朴吗啡的方式抑制丸剂和蔗糖的摄入，但不诱导行为刻板印象，并导致脑脊液中多巴胺浓度逐渐增加，而不是倒置的 U 形，并且不与摄食行为的作用相关。此外，虽然用低剂量顺式-氟哌丁醇（0.1mg）预处理可以逆转阿朴吗啡对蔗糖摄入的抑制作用，但胆囊收缩素八肽的抑制作用仅部分被顺式-氟哌丁醇逆转，并且需要更高剂量（0.8mg）。用 L-364,718 处理阻断胆囊收缩素-A 受体，而用 L-365,260 处理阻断胆囊收缩素-B 受体，阻断了胆囊收缩素八肽的抑制作用，而 L-364,718 本身就增加了摄入的蔗糖量。胆囊收缩素八肽对摄食行为的消耗性作用的抑制作用，由胆囊收缩素-A 受体介导，可能涉及除多巴胺能以外的机制。
