Disruptive effects of the prototypical cannabinoid Δ9-tetrahydrocannabinol and the fatty acid amide inhibitor URB-597 on go/no-go auditory discrimination performance and olfactory reversal learning in rats

Abstract

The effects of Δ⁹-tetrahydrocannabinol (Δ⁹-THC; 0.3, 1, 3 and 10 mg/kg), and the fatty acid amide hydrolysis inhibitor URB-597 (0.1 and 0.3 mg/kg), on auditory and olfactory go/no-go discrimination tasks were examined in rats. The aims were to assess (i) whether simple olfactory and auditory discrimination tasks are sensitive to cannabinoid interference and (ii) whether manipulation of endogenous cannabinoid levels with URB-597 might have adverse effects on perceptual and cognitive functions. Thirsty rats were trained to nose poke at a 'sniff port', where odours were briefly presented. After one odour (S+, lemon), licks made at an adjacent tube were rewarded with water, whereas licks after a second odour (S-, strawberry) were unrewarded. In an analogous auditory task, nose pokes produced an auditory S+ (beep) or S- (white noise). Δ⁹-THC and URB-597 impaired performance on the auditory but not the olfactory discrimination task. Auditory performance was still affected on the day after Δ⁹-THC (3 and 10 mg/kg) and URB-597 (0.3 mg/kg) exposure. Δ⁹-THC and URB-597 markedly impaired olfactory discrimination reversals without disrupting acquisition of the original discrimination. Rimonabant (CB1 antagonist; 3 mg/kg) reversed all Δ⁹-THC and URB-597 effects on auditory discriminations and olfactory discrimination reversals. These results confirm impairment of cognitive flexibility (reversal learning) by cannabinoids and show remarkable sensitivity of auditory discrimination performance to Δ⁹-THC and the augmented endocannabinoid signalling produced by URB-597.