Roles of the Endocannabinoid System in Learning and Memory

  • Giovanni MarsicanoEmail author
  • Pauline Lafenêtre
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 1)


The endocannabinoid system (ECS) plays a central role in the regulation of learning and memory processes. The fine-tuned regulation of neural transmission by the system is likely to be the mechanism underlying this important function. In this chapter, we review the data in the literature showing the direct involvement of the physiological activation of cannabinoid receptors in the modulation of different forms of learning and memory. When possible, we also address the likely mechanisms of this involvement. Finally, given the apparent special role of the ECS in the extinction of fear, we propose a reasonable model to assess how neuronal networks could be influenced by the endocannabinoids in these processes. Overall, the data reviewed indicate that, despite the enormous progress of recent years, much is still to be done to fully elucidate the mechanisms of the ECS influence on learning and memory processes.


Learning and memory Endocannabinoid system CB1 receptors Extinction Amygdala Model 





Basal nucleus of the amygdala


Basolateral amygdala


Calcium/calmodulin protein kinase II


Central nucleus of the amygdale


Conditioned response


Conditioned stimulus


Depolarization-induced suppression of inhibition


Endocannabinoid system


Fatty acid amide hydrolase


G protein-coupled receptor


Intercalated cell masses


Lateral nucleus of the amygdala


Long-term synaptic potentiation


Prefrontal cortex


Phosphatidylinositol 3-kinase




Unconditioned stimulus


  1. Adam AS, Wenger T, Csillag A (2008) The cannabinoid CB1 receptor antagonist rimonabant dose-dependently inhibits memory recall in the passive avoidance task in domestic chicks (Gallus domesticus). Brain Res Bull 76:272–274PubMedGoogle Scholar
  2. Alger E (2002) Retrograde signaling in the regulation of synaptic transmission: focus on endocannabinoids. Prog Neurobiol 68:247–286PubMedGoogle Scholar
  3. Arenos JD, Musty RE, Bucci DJ (2006) Blockade of cannabinoid CB1 receptors alters contextual learning and memory. Eur J Pharmacol 539:177–183PubMedGoogle Scholar
  4. Azad SC, Eder M, Marsicano G et al. (2003) Activation of the cannabinoid receptor type 1 decreases glutamatergic and GABAergic synaptic transmission in the lateral amygdala of the mouse. Learn Memory 10:116–128Google Scholar
  5. Azad SC, Monory K, Marsicano G et al. (2004) Circuitry for associative plasticity in the amygdala involves endocannabinoid signaling. J Neurosci 24:9953–9961PubMedGoogle Scholar
  6. Bacci A, Huguenard JR, Prince DA (2004) Long-lasting self-inhibition of neocortical interneurons mediated by endocannabinoids. Nature 431:312–316PubMedGoogle Scholar
  7. Bailey CH, Kandel ER, Si K (2004) The persistence of long-term memory: a molecular approach to self-sustaining changes in learning-induced synaptic growth. Neuron 44:49–57PubMedGoogle Scholar
  8. Barco A, Bailey CH, Kandel ER (2006) Common molecular mechanisms in explicit and implicit memory. J Neurochem 97:1520–1533PubMedGoogle Scholar
  9. Berretta S, Pantazopoulos H, Caldera M et al. (2005) Infralimbic cortex activation increases c-Fos expression in intercalated neurons of the amygdala. Neuroscience 132:943–953PubMedGoogle Scholar
  10. Bilkei-Gorzo A, Racz I, Valverde O et al. (2005) Early age-related cognitive impairment in mice lacking cannabinoid CB1 receptors. Proc Natl Acad Sci USA 102:15670–15675PubMedGoogle Scholar
  11. Bissiere S, Humeau Y, Luthi A (2003) Dopamine gates LTP induction in lateral amygdala by suppressing feedforward inhibition. Nat Neurosci 6:587–592PubMedGoogle Scholar
  12. Brower LP, Glazier SC (1975) Localization of heart poisons in the monarch butterfly. Science 188:19–25PubMedGoogle Scholar
  13. Bucherelli C, Baldi E, Mariottini C et al. (2006) Aversive memory reactivation engages in the amygdala only some neurotransmitters involved in consolidation. Learn Memory 13:426–430Google Scholar
  14. Bura SA, Castane A, Ledent C et al. (2007) Genetic and pharmacological approaches to evaluate the interaction between the cannabinoid and cholinergic systems in cognitive processes. Br J Pharmacol 150:758–765PubMedGoogle Scholar
  15. Cannich A, Wotjak CT, Kamprath K et al. (2004) CB1 cannabinoid receptors modulate kinase and phosphatase activity during extinction of conditioned fear in mice. Learn Memory 11:625–632Google Scholar
  16. Carlson G, Wang Y, Alger BE (2002) Endocannabinoids facilitate the induction of LTP in the hippocampus. Nat Neurosci 5:723–724PubMedGoogle Scholar
  17. Carter E, Wang XJ (2007) Cannabinoid-mediated disinhibition and working memory: dynamical interplay of multiple feedback mechanisms in a continuous attractor model of prefrontal cortex. Cereb Cortex 17(Suppl 1):i16–i26PubMedGoogle Scholar
  18. Castellano C, Rossi-Arnaud C, Cestari V et al. (2003) Cannabinoids and memory: animal studies. Curr Drug Targets CNS Neurol Disord 2:389–402PubMedGoogle Scholar
  19. Chevaleyre V, Takahashi KA, Castillo PE (2006) Endocannabinoid-mediated synaptic plasticity in the CNS. Annu Rev Neurosci 29:37–75PubMedGoogle Scholar
  20. Chhatwal JP, Davis M, Maguschak KA et al. (2005) Enhancing cannabinoid neurotransmission augments the extinction of conditioned fear. Neuropsychopharmacology 30:516–524PubMedGoogle Scholar
  21. Clarke JR, Rossato JI, Monteiro S et al. (2008) Posttraining activation of CB1 cannabinoid receptors in the CA1 region of the dorsal hippocampus impairs object recognition long-term memory. Neurobiol Learn Memory 90(2):374–381Google Scholar
  22. Collins DR, Pare D (1999a) Reciprocal changes in the firing probability of lateral and central medial amygdala neurons. J Neurosci 19:836–844PubMedGoogle Scholar
  23. Collins DR, Pare D (1999b) Spontaneous and evoked activity of intercalated amygdala neurons. Eur J Neurosci 11:3441–3448PubMedGoogle Scholar
  24. Cravatt BF, Demarest K, Patricelli MP et al. (2001) Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase. Proc Natl Acad Sci USA 98:9371–9376PubMedGoogle Scholar
  25. de Oliveira AL, de Oliveira LF, Camboim C et al. (2005) Amnestic effect of intrahippocampal AM251, a CB1-selective blocker, in the inhibitory avoidance, but not in the open field habituation task, in rats. Neurobiol Learn Memory 83:119–124Google Scholar
  26. Deadwyler SA, Hampson RE (2008) Endocannabinoids modulate encoding of sequential memory in the rat hippocampus. Psychopharmacology (Berl) 198:577–586Google Scholar
  27. Deadwyler SA, Goonawardena AV, Hampson RE (2007) Short-term memory is modulated by the spontaneous release of endocannabinoids: evidence from hippocampal population codes. Behav Pharmacol 18:571–580PubMedGoogle Scholar
  28. Debiec J, Ledoux JE, Nader K (2002) Cellular and systems reconsolidation in the hippocampus. Neuron 36:527–538PubMedGoogle Scholar
  29. Degroot A, Kofalvi A, Wade MR et al. (2006) CB1 receptor antagonism increases hippocampal acetylcholine release: site and mechanism of action. Mol Pharmacol 70:1236–1245PubMedGoogle Scholar
  30. Devane WA, Hanus L, Breuer A et al. (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258:1946–1949PubMedGoogle Scholar
  31. Di Marzo V, De Petrocellis L, Fezza F et al. (2002) Anandamide receptors. Prostag Leukot Ess Fatty Acids 66:377–391Google Scholar
  32. Domenici MR, Azad SC, Marsicano G et al. (2006) Cannabinoid receptor type 1 located on presynaptic terminals of principal neurons in the forebrain controls glutamatergic synaptic transmission. J Neurosci 26:5794–5799PubMedGoogle Scholar
  33. Dunning J, During MJ (2003) Molecular mechanisms of learning and memory. Expert Rev Mol Med 5:1–11PubMedGoogle Scholar
  34. Duvarci S, Nader K (2004) Characterization of fear memory reconsolidation. J Neurosci 24:9269–9275PubMedGoogle Scholar
  35. Floresco SB, Magyar O (2006) Mesocortical dopamine modulation of executive functions: beyond working memory. Psychopharmacology (Berl) 188:567–585Google Scholar
  36. Floresco SB, Magyar O, Ghods-Sharifi S et al. (2006) Multiple dopamine receptor subtypes in the medial prefrontal cortex of the rat regulate set-shifting. Neuropsychopharmacology 31:297–309PubMedGoogle Scholar
  37. Freund TF, Katona I, Piomelli D (2003) Role of endogenous cannabinoids in synaptic signaling. Physiol Rev 83:1017–1066PubMedGoogle Scholar
  38. Fride E (2005) Endocannabinoids in the central nervous system: from neuronal networks to behavior. Curr Drug Targets CNS Neurol Disord 4:633–642PubMedGoogle Scholar
  39. Fujiwara M, Egashira N (2004) New perspectives in the studies on endocannabinoid and cannabis: abnormal behaviors associate with CB1 cannabinoid receptor and development of therapeutic application. J Pharmacol Sci 96:362–366PubMedGoogle Scholar
  40. Gaoni Y, Mechoulam R (1964) Isolation, structure and partial synthesis of an active constituent of hashish. J Am Chem Soc 86:1646–1647Google Scholar
  41. Garcia J, Kimeldorf DJ, Koelling RA (1955) Conditioned aversion to saccharin resulting from exposure to gamma radiation. Science 122:157–158PubMedGoogle Scholar
  42. Harris JA, Westbrook RF (1998) Evidence that GABA transmission mediates context-specific extinction of learned fear. Psychopharmacology (Berl) 140:105–115Google Scholar
  43. Herry C, Ciocchi S, Senn V et al. (2008) Switching on and off fear by distinct neuronal circuits. Nature 454:600–606PubMedGoogle Scholar
  44. Hilário MRF, Clouse E, Yin HH et al. (2007) Endocannabinoid signaling is critical for habit formation. Front Integr Neurosci 1:6PubMedGoogle Scholar
  45. Hill MN, Froese LM, Morrish AC et al. (2006) Alterations in behavioral flexibility by cannabinoid CB1 receptor agonists and antagonists. Psychopharmacology (Berl) 187:245–259Google Scholar
  46. Holter SM, Kallnik M, Wurst W et al. (2005) Cannabinoid CB1 receptor is dispensable for memory extinction in an appetitively-motivated learning task. Eur J Pharmacol 510:69–74PubMedGoogle Scholar
  47. Howlett AC, Barth F, Bonner TI et al. (2002) International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 54:161–202PubMedGoogle Scholar
  48. Iversen L (2003a) Cannabis and the brain. Brain 126:1252–1270PubMedGoogle Scholar
  49. Iversen L (2003b) Comparing cannabis with tobacco: arithmetic does not add up. Br Med J 327:165Google Scholar
  50. Kamprath K, Wotjak CT (2004) Nonassociative learning processes determine expression and extinction of conditioned fear in mice. Learn Memory 11:770–786Google Scholar
  51. Kamprath K, Marsicano G, Tang J et al. (2006) Cannabinoid CB1 receptor mediates fear extinction via habituation-like processes. J Neurosci 26:6677–6686PubMedGoogle Scholar
  52. Kandel ER (2001) The molecular biology of memory storage: a dialog between genes and synapses. Biosci Rep 21:565–611PubMedGoogle Scholar
  53. Kandel ER, Schwartz JH, Jessel TM (2000) Principles of neural science. McGraw-Hill, New YorkGoogle Scholar
  54. Kobilo T, Hazvi S, Dudai Y (2007) Role of cortical cannabinoid CB1 receptor in conditioned taste aversion memory. Eur J Neurosci 25:3417–3421PubMedGoogle Scholar
  55. LeDoux JE (2000) Emotion circuits in the brain. Annu Rev Neurosci 23:155–184PubMedGoogle Scholar
  56. Lichtman AH (2000) SR 141716A enhances spatial memory as assessed in a radial-arm maze task in rats. Eur J Pharmacol 404:175–179PubMedGoogle Scholar
  57. Likhtik E, Pelletier JG, Paz R et al. (2005) Prefrontal control of the amygdala. J Neurosci 25:7429–7437PubMedGoogle Scholar
  58. Lin CH, Yeh SH, Lin CH et al. (2001) A role for the PI-3 kinase signaling pathway in fear conditioning and synaptic plasticity in the amygdala. Neuron 31:841–851PubMedGoogle Scholar
  59. Lin CH, Lee CC, Gean PW (2003a) Involvement of a calcineurin cascade in amygdala depotentiation and quenching of fear memory. Mol Pharmacol 63:44–52PubMedGoogle Scholar
  60. Lin CH, Yeh SH, Leu TH et al. (2003b) Identification of calcineurin as a key signal in the extinction of fear memory. J Neurosci 23:1574–1579PubMedGoogle Scholar
  61. Lin HC, Mao SC, Su CL et al. (2009) The role of prefrontal cortex CB1 receptors in the modulation of fear memory. Cereb Cortex 19(1):165–175PubMedGoogle Scholar
  62. Lu KT, Walker DL, Davis M (2001) Mitogen-activated protein kinase cascade in the basolateral nucleus of amygdala is involved in extinction of fear-potentiated startle. J Neurosci 21:RC162–RC166PubMedGoogle Scholar
  63. Lutz B (2002) Molecular biology of cannabinoid receptors. Prostag Leukot Ess Fatty Acids 66:123–142Google Scholar
  64. Maccarrone M, Valverde O, Barbaccia ML et al. (2002) Age-related changes of anandamide metabolism in CB1 cannabinoid receptor knockout mice: correlation with behaviour. Eur J Neurosci 15:1178–1186PubMedGoogle Scholar
  65. Maejima T, Ohno-Shosaku T, Kano M (2001) Endogenous cannabinoid as a retrograde messenger from depolarized postsynaptic neurons to presynaptic terminals. Neurosci Res 40:205–210PubMedGoogle Scholar
  66. Mallet PE, Beninger RJ (1998) The cannabinoid CB1 receptor antagonist SR141716A attenuates the memory impairment produced by delta9-tetrahydrocannabinol or anandamide. Psychopharmacology (Berl) 140:11–19Google Scholar
  67. Mansuy IM (2003) Calcineurin in memory and bidirectional plasticity. Biochem Biophys Res Commun 311:1195–1208PubMedGoogle Scholar
  68. Mansuy IM, Mayford M, Jacob B et al. (1998) Restricted and regulated overexpression reveals calcineurin as a key component in the transition from short-term to long-term memory. Cell 92:39–49PubMedGoogle Scholar
  69. Maren S (1999) Long-term potentiation in the amygdala: a mechanism for emotional learning and memory. Trends Neurosci 22:561–567PubMedGoogle Scholar
  70. Marks I, Tobena A (1990) Learning and unlearning fear: a clinical and evolutionary perspective. Neurosci Biobehav Rev 14:365–384PubMedGoogle Scholar
  71. Marsicano G, Lutz B (1999) Expression of the cannabinoid receptor CB1 in distinct neuronal subpopulations in the adult mouse forebrain. Eur J Neurosci 11:4213–4225PubMedGoogle Scholar
  72. Marsicano G, Lutz B (2006) Neuromodulatory functions of the endocannabinoid system. J Endocrinol Invest 29:27–46PubMedGoogle Scholar
  73. Marsicano G, Wotjak CT, Azad SC et al. (2002) The endogenous cannabinoid system controls extinction of aversive memories. Nature 418:530–534PubMedGoogle Scholar
  74. Martin M, Ledent C, Parmentier M et al. (2002) Involvement of CB1 cannabinoid receptors in emotional behaviour. Psychopharmacology (Berl) 159:379–387Google Scholar
  75. Massa F, Marsicano G, Hermann H et al. (2004) The endogenous cannabinoid system protects against colonic inflammation. J Clin Invest 113:1202–1209PubMedGoogle Scholar
  76. Matsuda LA, Lolait SJ, Brownstein MJ et al. (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561–564PubMedGoogle Scholar
  77. McDonald AJ (1998) Cortical pathways to the mammalian amygdala. Prog Neurobiol 55:257–332PubMedGoogle Scholar
  78. McGaugh JL (2000) Memory – a century of consolidation. Science 287:248–251PubMedGoogle Scholar
  79. McGaugh JL, Castellano C, Brioni J (1990) Picrotoxin enhances latent extinction of conditioned fear. Behav Neurosci 104:264–267PubMedGoogle Scholar
  80. Mechoulam R, Ben Shabat S, Hanus L et al. (1995) Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 50:83–90PubMedGoogle Scholar
  81. Mikics E, Barsy B, Barsvari B et al. (2005) Behavioral specificity of non-genomic glucocorticoid effects in rats: effects on risk assessment in the elevated plus-maze and the open-field. Horm Behav 48:152–162PubMedGoogle Scholar
  82. Mikics E, Dombi T, Barsvari B et al. (2006) The effects of cannabinoids on contextual conditioned fear in CB1 knockout and CD1 mice. Behav Pharmacol 17:223–230PubMedGoogle Scholar
  83. Milad MR, Quirk GJ (2002) Neurons in medial prefrontal cortex signal memory for fear extinction. Nature 420:70–74PubMedGoogle Scholar
  84. Myers KM, Davis M (2002) Behavioral and neural analysis of extinction. Neuron 36:567–584PubMedGoogle Scholar
  85. Myers KM, Davis M (2007) Mechanisms of fear extinction. Mol Psychiatry 12:120–150PubMedGoogle Scholar
  86. Nader K, Schafe GE, Ledoux JE (2000) The labile nature of consolidation theory. Nat Rev Neurosci 1:216–219PubMedGoogle Scholar
  87. Niyuhire F, Varvel SA, Thorpe AJ et al. (2007) The disruptive effects of the CB1 receptor antagonist rimonabant on extinction learning in mice are task-specific. Psychopharmacology (Berl) 191:223–231Google Scholar
  88. Pacher P, Batkai S, Kunos G (2006) The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 58:389–462PubMedGoogle Scholar
  89. Packard MG, McGaugh JL (1992) Double dissociation of fornix and caudate nucleus lesions on acquisition of two water maze tasks: further evidence for multiple memory systems. Behav Neurosci 106:439–446PubMedGoogle Scholar
  90. Pagotto U, Cervino C, Vicennati V et al. (2006) How many sites of action for endocannabinoids to control energy metabolism? Int J Obes (Lond) 30(Suppl 1):S39–S43Google Scholar
  91. Pare D, Quirk GJ, LeDoux JE (2004) New vistas on amygdala networks in conditioned fear. J Neurophysiol 92:1–9PubMedGoogle Scholar
  92. Pertwee RG (2008) The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol 153:199–215PubMedGoogle Scholar
  93. Pezze MA, Feldon J (2004) Mesolimbic dopaminergic pathways in fear conditioning. Prog Neurobiol 74:301–320PubMedGoogle Scholar
  94. Phelps EA, LeDoux JE (2005) Contributions of the amygdala to emotion processing: from animal models to human behavior. Neuron 48:175–187PubMedGoogle Scholar
  95. Quirk GJ, Mueller D (2008) Neural mechanisms of extinction learning and retrieval. Neuropsychopharmacology 33:56–72PubMedGoogle Scholar
  96. Ranganathan M, D'Souza DC (2006) The acute effects of cannabinoids on memory in humans: a review. Psychopharmacology (Berl) 188:425–444Google Scholar
  97. Reibaud M, Obinu MC, Ledent C et al. (1999) Enhancement of memory in cannabinoid CB1 receptor knock-out mice. Eur J Pharmacol 379:R1–R2PubMedGoogle Scholar
  98. Reich CG, Mohammadi MH, Alger BE (2008) Endocannabinoid modulation of fear responses: learning and state-dependent performance effects. J Psychopharmacol. 22:761–768Google Scholar
  99. Riedel G, Davies SN (2005) Cannabinoid function in learning, memory and plasticity. Handb Exp Pharmacol 168:445–477PubMedGoogle Scholar
  100. Rinaldi-Carmona M, Barth F, Heaulme M et al. (1994) SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Lett 350:240–244PubMedGoogle Scholar
  101. Robinson L, Killop-Smith S, Ross NL et al. (2008) Hippocampal endocannabinoids inhibit spatial learning and limit spatial memory in rats. Psychopharmacology (Berl) 198:551–563Google Scholar
  102. Rosenkranz JA, Grace AA (2002) Cellular mechanisms of infralimbic and prelimbic prefrontal cortical inhibition and dopaminergic modulation of basolateral amygdala neurons in vivo. J Neurosci 22:324–337PubMedGoogle Scholar
  103. Rosenkranz JA, Moore H, Grace AA (2003) The prefrontal cortex regulates lateral amygdala neuronal plasticity and responses to previously conditioned stimuli. J Neurosci 23:11054–11064PubMedGoogle Scholar
  104. Rueda-Orozco PE, Montes-Rodriguez CJ, Soria-Gomez E et al. (2008a) Impairment of endocannabinoids activity in the dorsolateral striatum delays extinction of behavior in a procedural memory task in rats. Neuropharmacology 55(1):55–62PubMedGoogle Scholar
  105. Rueda-Orozco PE, Soria-Gomez E, Montes-Rodriguez CJ et al. (2008b) A potential function of endocannabinoids in the selection of a navigation strategy by rats. Psychopharmacology (Berl) 198:565–576Google Scholar
  106. Sara SJ (2000) Retrieval and reconsolidation: toward a neurobiology of remembering. Learn Memory 7:73–84Google Scholar
  107. Shiflett MW, Rankin AZ, Tomaszycki ML et al. (2004) Cannabinoid inhibition improves memory in food-storing birds, but with a cost. Proc Biol Sci 271:2043–2048PubMedGoogle Scholar
  108. Soria G, Mendizabal V, Tourino C et al. (2005) Lack of CB1 cannabinoid receptor impairs cocaine self-administration. Neuropsychopharmacology 30:1670–1680PubMedGoogle Scholar
  109. Squire LR, Berq D, du Lac S et al. (2008) Fundamentals of Neuroscience, 3rd ednGoogle Scholar
  110. Stefani MR, Moghaddam B (2003) Distinct contributions of glutamate receptor subtypes to cognitive set-shifting abilities in the rat. Ann N Y Acad Sci 1003:464–467PubMedGoogle Scholar
  111. Stefani MR, Groth K, Moghaddam B (2003) Glutamate receptors in the rat medial prefrontal cortex regulate set-shifting ability. Behav Neurosci 117:728–737PubMedGoogle Scholar
  112. Straiker A, Mackie K (2007) Metabotropic suppression of excitation in murine autaptic hippocampal neurons. J Physiol 578:773–785PubMedGoogle Scholar
  113. Sugiura T, Kondo S, Sukagawa A et al. (1995) 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem Biophys Res Commun 215:89–97PubMedGoogle Scholar
  114. Suzuki A, Josselyn SA, Frankland PW et al. (2004) Memory reconsolidation and extinction have distinct temporal and biochemical signatures. J Neurosci 24:4787–4795PubMedGoogle Scholar
  115. Suzuki A, Mukawa T, Tsukagoshi A et al. (2008) Activation of LVGCCs and CB1 receptors required for destabilization of reactivated contextual fear memories. Learn Memory 15:426–433Google Scholar
  116. Sweatt JD (2001) The neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory. J Neurochem 76:1–10PubMedGoogle Scholar
  117. Takahashi RN, Pamplona FA, Fernandes MS (2005) The cannabinoid antagonist SR141716A facilitates memory acquisition and consolidation in the mouse elevated T-maze. Neurosci Lett 380:270–275PubMedGoogle Scholar
  118. Terranova JP, Storme JJ, Lafon N et al. (1996) Improvement of memory in rodents by the selective CB1 cannabinoid receptor antagonist, SR 141,716. Psychopharmacology (Berl) 126:165–172Google Scholar
  119. Thiemann G, Fletcher BC, Ledent C et al. (2007) The genetic versus pharmacological invalidation of the cannabinoid CB(1) receptor results in differential effects on 'non-associative' memory and forebrain monoamine concentrations in mice. Neurobiol Learn Memory 88:416–423Google Scholar
  120. Van Gaal LF, Rissanen AM, Scheen AJ et al. (2005) Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet 365:1389–1397PubMedGoogle Scholar
  121. Van Sickle MD, Duncan M, Kingsley PJ et al. (2005) Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science 310:329–332PubMedGoogle Scholar
  122. Varvel SA, Lichtman AH (2002) Evaluation of CB(1) Receptor Knockout Mice in the Morris Water Maze. J Pharmacol Exp Ther 301:915–924PubMedGoogle Scholar
  123. Varvel SA, Anum EA, Lichtman AH (2005) Disruption of CB(1) receptor signaling impairs extinction of spatial memory in mice. Psychopharmacology (Berl) 179:863–872Google Scholar
  124. Varvel SA, Cravatt BF, Engram AE et al. (2006) Fatty acid amide hydrolase (-/-) mice exhibit an increased sensitivity to the disruptive effects of anandamide or oleamide in a working memory water maze task. J Pharmacol Exp Ther 317:251–257PubMedGoogle Scholar
  125. Varvel SA, Wise LE, Niyuhire F et al. (2007) Inhibition of fatty-acid amide hydrolase accelerates acquisition and extinction rates in a spatial memory task. Neuropsychopharmacology 32:1032–1041PubMedGoogle Scholar
  126. Welzl H, D'Adamo P, Lipp HP (2001) Conditioned taste aversion as a learning and memory paradigm. Behav Brain Res 125:205–213PubMedGoogle Scholar
  127. White NM, McDonald RJ (2002) Multiple parallel memory systems in the brain of the rat. Neurobiol Learn Memory 77:125–184Google Scholar
  128. Wilson RI, Nicoll RA (2001) Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. Nature 410:588–592PubMedGoogle Scholar
  129. Winsauer PJ, Lambert P, Moerschbaecher JM (1999) Cannabinoid ligands and their effects on learning and performance in rhesus monkeys. Behav Pharmacol 10:497–511PubMedGoogle Scholar
  130. Wise LE, Iredale PA, Stokes RJ et al. (2007) Combination of rimonabant and donepezil prolongs spatial memory duration. Neuropsychopharmacology 32:1805–1812PubMedGoogle Scholar
  131. Wolff MC, Leander JD (2003) SR141716A, a cannabinoid CB1 receptor antagonist, improves memory in a delayed radial maze task. Eur J Pharmacol 477:213–217PubMedGoogle Scholar
  132. Wotjak CT (2005) Role of endogenous cannabinoids in cognition and emotionality. Mini Rev Med Chem 5:659–670PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.Group Molecular Mechanisms of Behavioural AdaptationResearch Centre INSERM U862 NeuroCentre Magendie Université Bordeaux 2BordeauxFrance

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