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Combined effects of THC and caffeine on working memory in rats.
Br J Pharmacol 2012; 165(8):2529-38BJ

Abstract

BACKGROUND AND PURPOSE

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.

EXPERIMENTAL APPROACH

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.

KEY RESULTS

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.

CONCLUSION AND IMPLICATIONS

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.

LINKED ARTICLES

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.

Authors+Show Affiliations

Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA. lpanlili@intra.nida.nih.gov

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

21699509

Citation

Panlilio, Leigh V., et al. "Combined Effects of THC and Caffeine On Working Memory in Rats." British Journal of Pharmacology, vol. 165, no. 8, 2012, pp. 2529-38.
Panlilio LV, Ferré S, Yasar S, et al. Combined effects of THC and caffeine on working memory in rats. Br J Pharmacol. 2012;165(8):2529-38.
Panlilio, L. V., Ferré, S., Yasar, S., Thorndike, E. B., Schindler, C. W., & Goldberg, S. R. (2012). Combined effects of THC and caffeine on working memory in rats. British Journal of Pharmacology, 165(8), pp. 2529-38. doi:10.1111/j.1476-5381.2011.01554.x.
Panlilio LV, et al. Combined Effects of THC and Caffeine On Working Memory in Rats. Br J Pharmacol. 2012;165(8):2529-38. PubMed PMID: 21699509.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combined effects of THC and caffeine on working memory in rats. AU - Panlilio,Leigh V, AU - Ferré,Sergi, AU - Yasar,Sevil, AU - Thorndike,Eric B, AU - Schindler,Charles W, AU - Goldberg,Steven R, PY - 2011/6/25/entrez PY - 2011/6/28/pubmed PY - 2012/7/28/medline SP - 2529 EP - 38 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 165 IS - 8 N2 - BACKGROUND AND PURPOSE: 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. EXPERIMENTAL APPROACH: 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. KEY RESULTS: 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. CONCLUSION AND IMPLICATIONS: 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. LINKED ARTICLES: 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. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/21699509/Combined_effects_of_THC_and_caffeine_on_working_memory_in_rats_ L2 - https://doi.org/10.1111/j.1476-5381.2011.01554.x DB - PRIME DP - Unbound Medicine ER -