McGregor I S, Dastur F N, McLellan R A, Brown R E
Department of Psychology, University of Sydney, NSW, Australia.
Eur J Pharmacol. 1996 Oct 10;313(1-2):43-9. doi: 10.1016/0014-2999(96)00511-0.
The present study investigated the effects of the cannabinoid receptor agonist CP 55,940 (1-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl) phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol) and the cannabinoid receptor antagonist SR 141716A (N-(piperidin-l-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1 H-pyrazole-3-carboxamide hydrochloride) on ultrasonic vocalizations, body temperature and activity in 11-13-day-old rat pups. Testing occurred in a 5-min session 30 min following drug administration. CP 55,940 produced a dose-dependent decrease in ultrasonic vocalizations, with a 1000-micrograms/kg dose causing an almost complete inhibition of calls. Doses of 100 and 1000 micrograms/kg of CP 55,940, but not 10 micrograms/kg, caused significant hypothermia in the pups and the 1000 micrograms/kg dose also inhibited activity. The cannabinoid receptor antagonist SR 141716A (20 mg/kg) reversed the effects of 1000 micrograms/kg CP 55,940 on ultrasonic vocalizations and body temperature, but the benzodiazepine receptor antagonist flumazenil (20 mg/kg), the dopamine D1 receptor antagonist SCH 23390 (0.5 mg/kg) and the opioid receptor antagonist naloxone (1 mg/kg) did not. When administered alone, SR 141716A (20 mg/kg) increased pup ultrasonic vocalizations without affecting body temperature or activity. These results indicate that cannabinoids modulate ultrasonic vocalization production in rat pups in a manner that is independent of hypothermia. The increase in ultrasonic vocalizations produced by SR 141716A is one of the first reported behavioural effects of this drug and suggests that the endogenous cannabinoid ligand anandamide may be involved in the regulation of ultrasonic vocalizations.
本研究调查了大麻素受体激动剂CP 55,940（(1-)-顺式-3-[2-羟基-4-(1,1-二甲基庚基)苯基]-反式-4-(3-羟丙基)环己醇）和大麻素受体拮抗剂SR 141716A（N-(哌啶-1-基)-5-(4-氯苯基)-1-(2,4-二氯苯基)-4-甲基-1H-吡唑-3-甲酰胺盐酸盐）对11至13日龄幼鼠超声发声、体温和活动的影响。给药30分钟后进行5分钟的测试。CP 55,940使超声发声呈剂量依赖性减少，1000微克/千克的剂量几乎完全抑制叫声。100和1000微克/千克剂量的CP 55,940（但不是10微克/千克）导致幼鼠体温显著降低，1000微克/千克剂量也抑制活动。大麻素受体拮抗剂SR 141716A（20毫克/千克）逆转了1000微克/千克CP 55,940对超声发声和体温的影响，但苯二氮䓬受体拮抗剂氟马西尼（20毫克/千克）、多巴胺D1受体拮抗剂SCH 23390（0.5毫克/千克）和阿片受体拮抗剂纳洛酮（1毫克/千克）则没有。单独给药时，SR 141716A（20毫克/千克）增加幼鼠超声发声，而不影响体温或活动。这些结果表明，大麻素以与体温降低无关的方式调节幼鼠的超声发声产生。SR 141716A引起的超声发声增加是该药物首次报道的行为效应之一，表明内源性大麻素配体花生四烯乙醇胺可能参与超声发声的调节。
