title: Combined effects of THC and caffeine on working memory in rats.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  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.affiliation: 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
authors.forename: Leigh V
authors.initials: LV
authors.lastname: Panlilio
authors.forename: Sergi
authors.initials: S
authors.lastname: Ferré
authors.forename: Sevil
authors.initials: S
authors.lastname: Yasar
authors.forename: Eric B
authors.initials: EB
authors.lastname: Thorndike
authors.forename: Charles W
authors.initials: CW
authors.lastname: Schindler
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldberg
mesh_terms: D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D013759:Dronabinol / Q000494:pharmacology*; D004357:Drug Synergism; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D043682:Receptor, Adenosine A1 / Q000502:physiology; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D043682:Receptor, Adenosine A1; C053907:8-cyclopentyl-1,3-dimethylxanthine; D002110:Caffeine; D013759:Dronabinol; D013806:Theophylline