Beijing Key Laboratory of Learning and Cognition, School of Psychology, Capital Normal University, Beijing 100048, China; Library, Capital Normal University, Beijing 100048, China.
Beijing Key Laboratory of Learning and Cognition, School of Psychology, Capital Normal University, Beijing 100048, China.
Pharmacol Biochem Behav. 2019 Jan;176:43-52. doi: 10.1016/j.pbb.2018.11.005. Epub 2018 Nov 14.
The non-selective muscarinic receptor agonist oxotremorine-M has been found to decrease impulsive choice in high-impulsive (HI) rats and increase impulsive choice in low-impulsive (LI) rats, but little is known about the muscarinic M receptor agonist N-desmethylclozapine (NDMC). This study investigated effects of NDMC on impulsive choice, and the effect of co-administration of NDMC with the dopamine D-like receptor antagonist SCH 23390 or D-like receptor antagonist raclopride on impulsive choice in HI and LI rats, characterized by basal levels of impulsive choice in a delay-discounting task. The results revealed that NDMC (1 and 2 mg/kg) significantly increased impulsive choice in HI, but not LI rats. SCH 23390 significantly promoted impulsive choice in HI rats at 0.01 mg/kg, and in LI rats at 0.0075 and 0.01 mg/kg. Moreover, SCH 23390 (0.005 and 0.0075 mg/kg) significantly inhibited the increase in impulsive choice induced by NDMC (1 mg/kg) in HI rats, whereas the increase in impulsive choice produced by SCH 23390 (0.0075 mg/kg) was significantly reversed by NDMC (1 mg/kg) in LI rats. Raclopride (0.04, 0.08, and 0.12 mg/kg) did not affect choice in both HI and LI rats, but significantly antagonized the increase in impulsive choice induced by NDMC (1 mg/kg) in HI rats. These findings suggest that D- and D-like receptors might be involved in different effects of the M receptor agonist on impulsive choice between HI and LI rats.
非选择性毒蕈碱受体激动剂氧托溴铵-M 已被发现可减少高冲动（HI）大鼠的冲动选择，并增加低冲动（LI）大鼠的冲动选择，但对毒蕈碱 M 受体激动剂 N-去甲氯氮平（NDMC）知之甚少。本研究探讨了 NDMC 对冲动选择的影响，以及 NDMC 与多巴胺 D 样受体拮抗剂 SCH 23390 或 D 样受体拮抗剂氯丙嗪共同给药对 HI 和 LI 大鼠冲动选择的影响，其特征是在延迟折扣任务中冲动选择的基础水平。结果表明，NDMC（1 和 2mg/kg）显著增加 HI 大鼠的冲动选择，但不增加 LI 大鼠的冲动选择。SCH 23390 显著促进 HI 大鼠在 0.01mg/kg 时的冲动选择，LI 大鼠在 0.0075 和 0.01mg/kg 时的冲动选择。此外，SCH 23390（0.005 和 0.0075mg/kg）显著抑制 NDMC（1mg/kg）引起的 HI 大鼠冲动选择增加，而 SCH 23390（0.0075mg/kg）引起的冲动选择增加被 NDMC（1mg/kg）在 LI 大鼠中显著逆转。氯丙嗪（0.04、0.08 和 0.12mg/kg）对 HI 和 LI 大鼠的选择均无影响，但显著拮抗 NDMC（1mg/kg）引起的 HI 大鼠冲动选择增加。这些发现表明，D 和 D 样受体可能参与了 M 受体激动剂对 HI 和 LI 大鼠冲动选择的不同影响。
