Improvement of memory in rodents by the selective CB1 cannabinoid receptor antagonist, SR 141716
- 302 Downloads
Social short-term memory in rodents is based on the recognition of a juvenile by an adult conspecific when the juvenile is presented on two successive occasions. Cannabimimetics are claimed to induce memory deficits in both humans and animals. In the brain, they mainly bind to CB1 receptors for which anandamide is a purported endogenous ligand. SR 141716, a specific antagonist of CB1 receptors, dose-dependently reverses biochemical and pharmacological effects of cannabimimetics. More particularly, it antagonizes the inhibition of hippocampal long-term potentiation induced by WIN 55,212-2 and anandamide, and it increases arousal when given alone. The present experiments study the ability of SR 141716 (from 0.03 to 3 mg/kg SC) to facilitate short-term olfactory memory in the social recognition test in rodents. SR 141716 improved social recognition in a long intertrial paradigm with a threshold dose of 0.1 mg/kg SC. At 1 mg/kg, it antagonized the memory disturbance elicited by retroactive inhibition. Scopolamine (0.06 mg/kg IP) partially reversed its memory-enhancing effect. Moreover, SR 141716 reduced memory deficit in aged rats (0.03–0.1 mg/kg) and mice (0.3–1 mg/kg). As SR 141716 is not known to exhibit any pharmacological activity which is not mediated by CB1 receptors, the results strongly support the concept that blockade of CB1 receptors plays an important role in consolidation of short-term memory in rodents and suggest there may be a role for an endogenous cannabinoid agonist tone (anandaminergic) in forgetting.
Key wordsSocial recognition Memory Rat Mouse Cannabimimetic Cannabinoid antagonist SR 141716 Ageing
Unable to display preview. Download preview PDF.
- Bartus RT, Dean RL, Beer B, Lippa AS (1982) The cholinergic hypothesis of geriatric memory dysfunction. Science 217:408–417Google Scholar
- Childers SR, Roy MB, Stark S (1993) G-protein-mediated activities of cannabinoid receptors in cerebellar granule cells. Soc Neurosci Abstr 19:1388Google Scholar
- Darley CF, Tinklenberg JR, Roth WT, Hollister LE, Atkinson RC (1973) Influence of marihuana on storage and retrieval processes in memory. Mem Cognit 1:196–200Google Scholar
- Hovland CI (1951) Human learning and retention. In: Stevens SS (ed) Handbook of experimental psychology, 2nd edn. John Wiley, New York, pp 613–689Google Scholar
- Lichtman AH, Martin BR (1995) The novel cannabinoid antagonist SR 141716 A blocks Δ9-THC impairment of working memory in rats. Soc Neurosci Abstr 21:167Google Scholar
- Mallet PE, Beninger RJ (1995) The endogenous cannabinoid receptor agonist anandamide impairs working memory but not reference memory in rats. Soc Neurosci Abstr 21:167Google Scholar
- Westlake TM, Howlett AC, Bonner TI, Matsuda LA, Herkenham M (1994) Cannabinoid receptor binding and messenger RNA expression in human brain: an in vitro receptor autoradiography and in situ hybridization histochemistry study of normal aged and Alzheimer's brains. Neuroscience 63:637–652CrossRefPubMedGoogle Scholar