McAllister K H
Novartis Pharma, Nervous System Department, WSJ-106.241, 4002 Basel, Switzerland.
Psychopharmacology (Berl). 2001 Jun;155(4):379-88. doi: 10.1007/s002130100736.
alpha 2 adrenoceptor mechanisms appear to play a role in the performance of delayed response working memory tasks but there are contradictory results.
To investigate whether RX 821002 (2-methoxy-idazoxan) and yohimbine and would affect the performance of the delayed non-matching-to-position (DNMTP) task in rats and compare the effects to those of the cholinergic antagonist scopolamine.
Male Lister Hooded rats trained to criterion in an operant DNMTP task (0-48 s delay intervals) were administered vehicle, RX 821002 (0.3, 1, 3 mg/kg s.c.), yohimbine (1, 3 mg/kg. s.c.) or scopolamine (0.05 mg/kg, s.c.). Together with choice accuracy, the motor performance of the task was measured.
It was found that: (1) both RX 821002 and yohimbine statistically significantly reduced choice accuracy dose- and delay-dependently and in a similar magnitude to that of scopolamine while modifying the motor aspects of task performance delay-independently and (2) RX 821002 produced mainly rate-decreasing effects. Yohimbine exerted stimulatory effects at the lowest dose and rate-decreasing effects at the highest dose, a profile consistent with that already described in operant tasks.
The results confirm that alpha 2 antagonists delay-dependently impair choice accuracy in a delayed-response paradigm.
α2肾上腺素能受体机制似乎在延迟反应工作记忆任务的执行中发挥作用,但存在相互矛盾的结果。
研究RX 821002(2-甲氧基-咪唑克生)和育亨宾是否会影响大鼠的延迟位置不匹配(DNMTP)任务的表现,并将其效果与胆碱能拮抗剂东莨菪碱的效果进行比较。
对经过操作性DNMTP任务(0-48秒延迟间隔)训练达到标准的雄性利斯特戴帽大鼠给予溶剂、RX 821002(0.3、1、3毫克/千克,皮下注射)、育亨宾(1、3毫克/千克,皮下注射)或东莨菪碱(0.05毫克/千克,皮下注射)。除了选择准确性外,还测量了任务的运动表现。
发现:(1)RX 821002和育亨宾在统计学上均显著降低选择准确性,且呈剂量和延迟依赖性,其程度与东莨菪碱相似,同时独立于延迟改变任务表现的运动方面;(2)RX 821002主要产生降低速率的作用。育亨宾在最低剂量时产生刺激作用,在最高剂量时产生降低速率的作用,这一情况与在操作性任务中已经描述的情况一致。
结果证实α2拮抗剂在延迟反应范式中会延迟依赖性地损害选择准确性。