Borisenko S A, Meng Q H, Rauhala P, Männistö P T
Department of Pharmacology and Toxicology, University of Helsinki, Finland.
Pharmacol Toxicol. 1996 May;78(5):354-60. doi: 10.1111/j.1600-0773.1996.tb01388.x.
We studied effects of anxiogenic and anxiolytic compounds on the electric self-stimulation of the medial fore-brain bundle in male rats to find out if there is a link between reward and anxiety-related behaviours. The cholecystokinin agonist, caerulein (25-100 micrograms/kg) and the 5-HT agonist 1-(3-chlorophenyl)piperazine (0.2-1 mg/kg) dose-dependently inhibited the electric self-stimulation. The 5-HT2A antagonist, ketanserin, at 2.5 mg/kg, increased the self-stimulation at high currents but not at threshold current. The 5-HT3 antagonist ondansetron (10 and 100 micrograms/kg). The alpha 1-adrenergic antagonist, prazosin (0.125 and 0.5 mg/kg), the beta-adrenergic antagonist, propranolol (5 and 10 mg/kg) and the alpha 2-adreno-receptor antagonist, atipamezole (4 mg/kg), did not affect the self-stimulation. Nor did the benzodiazepine agonist, diazepam (5-15 mg/kg), a benzodiazepine receptor antagonist flumazenil (at 10 and 25 mg/kg) or the inverse agonist of benzodiazepine receptors, N-methyl-beta-carboline-3-carboxamide (10 and 20 mg/kg), cause any substantial changes of the self-stimulation. We conclude that only two anxiolytic drugs (caerulein and 1-(3-chlorophenyl)piperazine) suppress the electric self-stimulation. These findings indicate that anxiogenicity as such is not able to weaken the hypothalamic electric self-stimulation. Anxiety and reward are apparently mediated through separate neural pathways.
我们研究了致焦虑和抗焦虑化合物对雄性大鼠内侧前脑束电自我刺激的影响，以确定奖赏与焦虑相关行为之间是否存在联系。胆囊收缩素激动剂雨蛙肽（25 - 100微克/千克）和5 - 羟色胺激动剂1 -（3 - 氯苯基）哌嗪（0.2 - 1毫克/千克）剂量依赖性地抑制电自我刺激。5 - 羟色胺2A拮抗剂酮色林，在2.5毫克/千克时，在高电流下增加自我刺激，但在阈电流时不增加。5 - 羟色胺3拮抗剂昂丹司琼（10和100微克/千克）。α1肾上腺素能拮抗剂哌唑嗪（0.125和0.5毫克/千克）、β肾上腺素能拮抗剂普萘洛尔（5和10毫克/千克）以及α2肾上腺素能受体拮抗剂阿替美唑（4毫克/千克），均不影响自我刺激。苯二氮䓬激动剂地西泮（5 - 15毫克/千克）、苯二氮䓬受体拮抗剂氟马西尼（10和25毫克/千克）或苯二氮䓬受体反向激动剂N - 甲基 - β - 咔啉 - 3 - 甲酰胺（10和20毫克/千克），也未引起自我刺激的任何显著变化。我们得出结论，只有两种抗焦虑药物（雨蛙肽和1 -（3 - 氯苯基）哌嗪）抑制电自我刺激。这些发现表明，焦虑本身并不能削弱下丘脑电自我刺激。焦虑和奖赏显然是通过不同的神经通路介导的。
