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Combined effects of THC and caffeine on working memory in rats.

Leigh V Panlilio, Sergi Ferré, Sevil Yasar, Eric B. Thorndike, Charles W. Schindler, Steven R Goldberg

British Journal of Pharmacology April 2012 DOI: 10.1111/j.1476-5381.2011.01554.x (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Rodent experimental study Peer reviewed
Population Rats
Interventions THC Caffeine CPT SCH58261
Dose THC 0, 1 and 3 mg/kg i.p.; caffeine 0, 1, 3 and 10 mg/kg i.p.; CPT 0, 3 and 10 mg/kg; SCH58261 0 and 5 mg/kg
Topics Cannabis
Key findings THC at 3 mg/kg impaired working memory in rats, and combining a subthreshold THC dose (1 mg/kg) with caffeine (10 mg/kg) or the adenosine A1 antagonist CPT (10 mg/kg) significantly impaired memory despite leaving rehearsal-like behavior unchanged. Caffeine did not counteract THC-induced memory deficits but exacerbated them, a result the authors say is consistent with adenosine A1 receptors modulating cannabinoid signaling in the hippocampus.

Abstract

Cannabis and caffeine are two of the most widely used psychoactive substances. Δ(9) -Tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, induces deficits in short-term memory. Caffeine, a non-selective adenosine receptor antagonist, attenuates some memory deficits, but there have been few studies addressing the effects of caffeine and THC in combination. Here, we evaluate the effects of these drugs using a rodent model of working memory. Rats were given THC (0, 1 and 3 mg·kg(-1) , i.p.) along with caffeine (0, 1, 3 and 10 mg·kg(-1) , i.p.), the selective adenosine A(1) -receptor antagonist CPT (0, 3 and 10 mg·kg(-1) ) or the selective adenosine A(2A) -receptor antagonist SCH58261 (0 and 5 mg·kg(-1) ) and were tested with a delayed non-matching-to-position procedure in which behaviour during the delay was automatically recorded as a model of memory rehearsal. THC alone produced memory deficits at 3 mg·kg(-1) . The initial exposure to caffeine (10 mg·kg(-1) ) disrupted the established pattern of rehearsal-like behaviour, but tolerance developed rapidly to this effect. CPT and SCH58261 alone had no significant effects on rehearsal or memory. When a subthreshold dose of THC (1 mg·kg(-1) ) was combined with caffeine (10 mg·kg(-1) ) or CPT (10 mg·kg(-1) ), memory performance was significantly impaired, even though performance of the rehearsal-like pattern was not significantly altered. Caffeine did not counteract memory deficits induced by THC but actually exacerbated them. These results are consistent with recent findings that adenosine A(1) receptors modulate cannabinoid signalling in the hippocampus. This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7.

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