A comparison of cannabidiolic acid with other treatments for anticipatory nausea using a rat model of contextually elicited conditioned gaping

作者：Rock Erin M; Limebeer Cheryl L; Navaratnam Roshan; Sticht Martin A; Bonner Natasha; Engeland Kristin; Downey Rachel; Morris Heather; Jackson Meagan; Parker Linda A^*

来源：Psychopharmacology, 2014, 231(16): 3207-3215.

DOI：10.1007/s00213-014-3498-1

• Cannabidiolic acid
• Ondansetron
• Chlordiazepoxide
• Delta(9)-tetrahydrocannabinol
• Tetrahydrocannabinolic acid
• Conditioned fear
• Nausea
• Anticipatory nausea
• Activity

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. %26lt;br%26gt;The potential of ondansetron (OND), Delta(9)-tetrahydrocannabinol (THC), chlordiazepoxide (CDP), CBDA, and co-administration of CBDA and tetrahydrocannabinolic acid (THCA) to reduce AN and modify locomotor activity was evaluated. %26lt;br%26gt;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 mu g/kg), and THCA (5 mu g/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. %26lt;br%26gt;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. %26lt;br%26gt;CBDA has therapeutic potential as a highly potent and selective treatment for AN without psychoactive or locomotor effects.

• 出版日期2014-8