Previous studies have revealed that cannabinoids have detrimental effects on learning and memory in humans and animals. Infusion of the exogenous Cannabinoid agonists including D9-tetrahydrocannabinol (D9-THC), HU210 and WIN-55, 212-2 (WIN-2) in animals has consistently been shown to induce deficits in spatial learning and memory. CB1 receptors are evident in the hippocampus and prefrontal cortex; brain areas involved in spatial learning and memory processes. The main aim of this study was to determine the mechanisms underlying these Cannabinoid-induced effects on spatial learning and memory. Lister Hooded rats were used to study the effects of cannabinoids in a sequence of experiments using the water maze. A novel paradigm to test place preference in the water maze was developed and it was revealed that D9-THC induced place aversion whereas WIN-2 had no effect. These aversive properties of D9-THC along with the non-spatial, non-CB1receptor effects of HU210 in reference memory may confound the results obtained for spatial learning and memory. By contrast, WIN-2 deficits would be a genuine result of spatial impairments. WIN-2 induced differential effects on working and reference memory. Reversal with the CB1 antagonist AM281 and vanilloid receptor (VR1) antagonist Iodo-RTX suggest that the WIN-2 effects are mediated via a non-CB 1/non-VR1 receptor located in the hippocampus. The WIN-2 effects could also be mediated via a possible interaction with the cholinergic system, as the cholinesterase inhibitor Rivastigmine was able to reverse the deficit. In addition to exogenous cannabinoids, using the CB1 antagonist SR141716A (SR) observed that endocannabinoids also impaired spatial learning and memory, with SR acting like an inverse agonist. In conclusion both cannabinoids and endocannabinoids impair spatial learning and memory in the water maze, and these deficits may occur via interactions with other neurotransmitter systems. However, whether these actions are mediated via the CB1 or a non-CB1 mechanism still remains unclear.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:415682 |
| Date | January 2004 |
| Creators | Robinson, Lianne |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU193926 |
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