Rock Erin M, Limebeer Cheryl L, Navaratnam Roshan, Sticht Martin A, Bonner Natasha, Engeland Kristin, Downey Rachel, Morris Heather, Jackson Meagan, Parker Linda A
Department of Psychology and Collaborative Neuroscience Program, University of Guelph, 50 Stone Rd E, Guelph, ON, N1G 2W1, Canada.
Psychopharmacology (Berl). 2014 Aug;231(16):3207-15. doi: 10.1007/s00213-014-3498-1. Epub 2014 Mar 5.
The effectiveness of cannabidiolic acid (CBDA) was compared with other potential treatments for anticipatory nausea (AN), using a rat model of contextually elicited conditioned gaping reactions.
The potential of ondansetron (OND), Δ(9)-tetrahydrocannabinol (THC), chlordiazepoxide (CDP), CBDA, and co-administration of CBDA and tetrahydrocannabinolic acid (THCA) to reduce AN and modify locomotor activity was evaluated.
Following four pairings of a novel context with lithium chloride (LiCl), the rats were given a test for AN. On the test trial, they received pretreatment injections of the following: vehicle, OND (0.1 or 1.0 mg/kg), THC (0.5 mg/kg), CBDA (0.0001, 0.001, 0.01, 0.1 mg/kg or 1.0 mg/kg), CDP (1, 5, or 10 mg/kg) or co-administration of subthreshold doses of CBDA (0.1 μg/kg), and THCA (5 μg/kg). Immediately following the AN test trial in all experiments, rats were given a 15 min locomotor activity test. Finally, the potential of CBDA (0.001, 0.01, 0.1, and 1 mg/kg) to attenuate conditioned freezing to a shock-paired tone was assessed.
THC, CBDA, and CDP, but not OND, reduced contextually elicited gaping reactions. Co-administration of subthreshold doses of CBDA and THCA also suppressed AN, and this effect was blocked by pretreatment with either a cannabinoid receptor 1 (CB1) receptor antagonist or a 5-hydroxytryptamine 1A (5-HT1A) receptor antagonist. CDP (but not CBDA, THC or CBDA and THCA) also suppressed locomotor activity at effective doses. CBDA did not modify the expression of conditioned fear.
CBDA has therapeutic potential as a highly potent and selective treatment for AN without psychoactive or locomotor effects.
使用情境引发的条件性张口反应大鼠模型，将大麻二酚酸（CBDA）的有效性与其他预期性恶心（AN）的潜在治疗方法进行比较。
评估昂丹司琼（OND）、Δ⁹-四氢大麻酚（THC）、氯氮卓（CDP）、CBDA以及CBDA与四氢大麻酚酸（THCA）联合给药减少AN和改变运动活动的潜力。
在将新环境与氯化锂（LiCl）进行四次配对后，对大鼠进行AN测试。在测试试验中，它们接受以下预处理注射：赋形剂、OND（0.1或1.0mg/kg）、THC（0.5mg/kg）、CBDA（0.0001、0.001、0.01、0.1mg/kg或1.0mg/kg）、CDP（1、5或10mg/kg）或阈下剂量的CBDA（0.1μg/kg）和THCA（5μg/kg）联合给药。在所有实验的AN测试试验后，立即对大鼠进行15分钟的运动活动测试。最后，评估CBDA（0.001、0.01、0.1和1mg/kg）减弱对与电击配对的音调的条件性僵住反应的潜力。
THC、CBDA和CDP可减少情境引发的张口反应，而OND则不能。阈下剂量的CBDA和THCA联合给药也可抑制AN，且这种作用可被大麻素受体1（CB1）受体拮抗剂或5-羟色胺1A（5-HT1A）受体拮抗剂预处理所阻断。有效剂量的CDP（而非CBDA、THC或CBDA与THCA联合给药）也可抑制运动活动。CBDA未改变条件性恐惧的表达。
CBDA作为一种高效且选择性的AN治疗方法具有治疗潜力，且无精神活性或运动效应。
