Arnold J C, Hunt G E, McGregor I S
Department of Psychology, University of Sydney, New South Wales, Australia.
Life Sci. 2001 Nov 21;70(1):97-108. doi: 10.1016/s0024-3205(01)01366-2.
Lewis rats were trained to self-stimulate the medial forebrain bundle (MFB) using a rate-frequency paradigm. They were then tested for the effects of the cannabinoid receptor agonist CP 55,940, the selective cannabinoid receptor antagonist SR 141716 and the dopamine D1 receptor antagonist SCH 23390. CP 55,940 (0, 10, 25 and 50 microg/kg i.p.) had no effect on MFB self-stimulation behaviour as assessed by the M50, the stimulation frequency at which half-maximal response rates were obtained. With SR 141716, only a very high dose (20 mg/kg i.p.) caused a significant inhibition of the rewarding efficacy of the stimulation. This was seen as an increase in the M50. All other doses of SR 141716 (0, 1, 3, 10 mg/kg i.p.) were ineffective in modulating the M50. By comparison, a relatively low dose (0.06 mg/kg i.p.) of SCH 23390 caused a large increase in M50. These results indicate a relatively modest influence, if any at all, of exogenous or endogenous cannabinoids on reward-relevant neurotransmission.
采用频率-速率范式训练Lewis大鼠自我刺激内侧前脑束(MFB)。然后测试大麻素受体激动剂CP 55,940、选择性大麻素受体拮抗剂SR 141716和多巴胺D1受体拮抗剂SCH 23390的作用。CP 55,940(0、10、25和50微克/千克腹腔注射)对MFB自我刺激行为无影响,这是通过M50评估得出的,M50即获得半数最大反应速率时的刺激频率。使用SR 141716时,只有非常高的剂量(20毫克/千克腹腔注射)会显著抑制刺激的奖赏效力,表现为M50增加。所有其他剂量的SR 141716(0、1、3、10毫克/千克腹腔注射)在调节M50方面均无效。相比之下,相对较低剂量(0.06毫克/千克腹腔注射)的SCH 23390会导致M50大幅增加。这些结果表明,外源性或内源性大麻素对与奖赏相关的神经传递的影响相对较小,即便有影响也是微乎其微。