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Gene Review

Cnr1  -  cannabinoid receptor 1 (brain)

Rattus norvegicus

Synonyms: Brain-type cannabinoid receptor, CB-R, CB1, Cannabinoid receptor 1, Skr6
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Disease relevance of Cnr1


Psychiatry related information on Cnr1

  • Potential role of the cannabinoid receptor CB1 in rapid eye movement sleep rebound [6].
  • Unlike sleep deprivation, sleep rebound significantly increased CB1R protein while decreasing mRNA [7].
  • The effects of the highest dose of AMG-3 on spontaneous activity and on the self-stimulation paradigm were completely reversed by pre-treatment with the CB1 receptor antagonist AM-251 [8].
  • An acute dose (100 microg/kg) of the CB1 agonist HU-210 suppressed locomotor activity, and had an anxiogenic-like effect on the elevated plus-maze [9].
  • The effects of chronic exposure to cannabinoids on short-term memory in rats were assessed during repeated daily injections of an initially debilitating dose (3.75 mg/kg) of the potent CB1 cannabinoid receptor ligand, WIN 55,212-2 [10].

High impact information on Cnr1


Chemical compound and disease context of Cnr1


Biological context of Cnr1


Anatomical context of Cnr1

  • We have studied the effects of two cannabinoid receptor agonists, WIN 55,212-2 and cannabinol, on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in the C6 glioma cell line [1].
  • These data suggest that selective cannabinoid CB1 receptor activation, by inhibiting iNOS expression and NO overproduction in glial cells, might be helpful in NO-mediated inflammation leading to neurodegeneration [1].
  • Cellular coexistence of 5-HT3A and CB1 transcripts in interneurons of the cortex, hippocampal formation, and amygdala suggest possible interactions between the cannabinoid and serotonergic systems at the level of GABA neurotransmission in brain areas involved in cognition, memory, and emotion [22].
  • Furthermore, very few neurons (approximately 5%) in the peptidergic (defined as calcitonin gene-related peptide- or substance P-immunoreactive) or the isolectin B4-binding sensory neuron populations contained CB1 mRNA [23].
  • In vivo and in vitro treatment with the synthetic cannabinoid CP55, 940 decreases the in vitro migration of macrophages in the rat: involvement of both CB1 and CB2 receptors [24].

Associations of Cnr1 with chemical compounds


Physical interactions of Cnr1


Regulatory relationships of Cnr1

  • Semi-quantitative analysis demonstrated that, depending on the hippocampal layer, 72-88% of CB1-expressing interneurons coexpress the 5-HT3A subunit [25].
  • Cannabinoid CB1 receptors in the brain are expressed on axon terminals presynaptic to neurons that express fatty acid amide hydrolase (FAAH) [29].
  • Recent evidence indicates the existence of cannabinoid receptors distinct from CB1 or CB2 that are inhibited by SR-141716 but not by other CB1 antagonists such as AM251 [30].
  • Data indicate that activation of JNK and p38 mitogen-activated protein kinase may be responsible for some of the cellular responses elicited by the CB(1) cannabinoid receptor [27].
  • We conclude that the cellular and subcellular pattern of type 1 cannabinoid receptor expression during early post-natal life is similar to the adult pattern and type 1 cannabinoid receptors are expressed on the cholecystokinin-containing axons as soon as synapse formation begins [31].

Other interactions of Cnr1


Analytical, diagnostic and therapeutic context of Cnr1


  1. Selective cannabinoid CB1 receptor-mediated inhibition of inducible nitric oxide synthase protein expression in C6 rat glioma cells. Esposito, G., Izzo, A.A., Di Rosa, M., Iuvone, T. J. Neurochem. (2001) [Pubmed]
  2. Delta-9-tetrahydrocannabinol protects cardiac cells from hypoxia via CB2 receptor activation and nitric oxide production. Shmist, Y.A., Goncharov, I., Eichler, M., Shneyvays, V., Isaac, A., Vogel, Z., Shainberg, A. Mol. Cell. Biochem. (2006) [Pubmed]
  3. Local application of the cannabinoid receptor agonist, WIN 55,212-2, to spinal trigeminal nucleus caudalis differentially affects nociceptive and non-nociceptive neurons. Papanastassiou, A.M., Fields, H.L., Meng, I.D. Pain (2004) [Pubmed]
  4. CB1 and CB2 cannabinoid receptors are implicated in inflammatory pain. Clayton, N., Marshall, F.H., Bountra, C., O'Shaughnessy, C.T. Pain (2002) [Pubmed]
  5. Inhibition of inflammatory hyperalgesia by activation of peripheral CB2 cannabinoid receptors. Quartilho, A., Mata, H.P., Ibrahim, M.M., Vanderah, T.W., Porreca, F., Makriyannis, A., Malan, T.P. Anesthesiology (2003) [Pubmed]
  6. Potential role of the cannabinoid receptor CB1 in rapid eye movement sleep rebound. Navarro, L., Martínez-vargas, M., Murillo-rodríguez, E., Landa, A., Méndez-díaz, M., Prospéro-garcía, O. Neuroscience (2003) [Pubmed]
  7. Sleep modulates cannabinoid receptor 1 expression in the pons of rats. Martínez-Vargas, M., Murillo-Rodríguez, E., González-Rivera, R., Landa, A., Méndez-Díaz, M., Prospro-García, O., Navarro, L. Neuroscience (2003) [Pubmed]
  8. Behavioral pharmacological properties of a novel cannabinoid 1',1'-dithiolane delta8-THC analog, AMG-3. Antoniou, K., Galanopoulos, A., Vlachou, S., Kourouli, T., Nahmias, V., Thermos, K., Panagis, G., Daifoti, Z., Marselos, M., Papahatjis, D., Spyraki, C. Behavioural pharmacology. (2005) [Pubmed]
  9. Corticotropin-releasing hormone (CRH) mRNA expression in rat central amygdala in cannabinoid tolerance and withdrawal: evidence for an allostatic shift? Caberlotto, L., Rimondini, R., Hansson, A., Eriksson, S., Heilig, M. Neuropsychopharmacology (2004) [Pubmed]
  10. Tolerance to the memory disruptive effects of cannabinoids involves adaptation by hippocampal neurons. Hampson, R.E., Simeral, J.D., Kelly, E.J., Deadwyler, S.A. Hippocampus. (2003) [Pubmed]
  11. Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis. Schuchmann, S., Schmitz, D., Rivera, C., Vanhatalo, S., Salmen, B., Mackie, K., Sipilä, S.T., Voipio, J., Kaila, K. Nat. Med. (2006) [Pubmed]
  12. Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. Wilson, R.I., Nicoll, R.A. Nature (2001) [Pubmed]
  13. Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Zygmunt, P.M., Petersson, J., Andersson, D.A., Chuang, H., Sørgård, M., Di Marzo, V., Julius, D., Högestätt, E.D. Nature (1999) [Pubmed]
  14. Endocannabinoids acting at cannabinoid-1 receptors regulate cardiovascular function in hypertension. Bátkai, S., Pacher, P., Osei-Hyiaman, D., Radaeva, S., Liu, J., Harvey-White, J., Offertáler, L., Mackie, K., Rudd, M.A., Bukoski, R.D., Kunos, G. Circulation (2004) [Pubmed]
  15. Cannabinoids and neuroprotection in global and focal cerebral ischemia and in neuronal cultures. Nagayama, T., Sinor, A.D., Simon, R.P., Chen, J., Graham, S.H., Jin, K., Greenberg, D.A. J. Neurosci. (1999) [Pubmed]
  16. Cannabinoid receptor-independent inhibition by cannabinoid agonists of the peripheral 5-HT3 receptor-mediated von Bezold-Jarisch reflex. Godlewski, G., Göthert, M., Malinowska, B. Br. J. Pharmacol. (2003) [Pubmed]
  17. LY320135, a novel cannabinoid CB1 receptor antagonist, unmasks coupling of the CB1 receptor to stimulation of cAMP accumulation. Felder, C.C., Joyce, K.E., Briley, E.M., Glass, M., Mackie, K.P., Fahey, K.J., Cullinan, G.J., Hunden, D.C., Johnson, D.W., Chaney, M.O., Koppel, G.A., Brownstein, M. J. Pharmacol. Exp. Ther. (1998) [Pubmed]
  18. Evidence for an interaction between CB1 cannabinoid and melanocortin MCR-4 receptors in regulating food intake. Verty, A.N., McFarlane, J.R., McGregor, I.S., Mallet, P.E. Endocrinology (2004) [Pubmed]
  19. Endocannabinoid system in frog and rodent testis: type-1 cannabinoid receptor and fatty acid amide hydrolase activity in male germ cells. Cobellis, G., Cacciola, G., Scarpa, D., Meccariello, R., Chianese, R., Franzoni, M.F., Mackie, K., Pierantoni, R., Fasano, S. Biol. Reprod. (2006) [Pubmed]
  20. Expression and biological effects of CB1 cannabinoid receptor in rat parotid gland. Busch, L., Sterin-Borda, L., Borda, E. Biochem. Pharmacol. (2004) [Pubmed]
  21. Down-regulation of cannabinoid-1 (CB-1) receptors in specific extrahypothalamic regions of rats with dietary obesity: a role for endogenous cannabinoids in driving appetite for palatable food? Harrold, J.A., Elliott, J.C., King, P.J., Widdowson, P.S., Williams, G. Brain Res. (2002) [Pubmed]
  22. Cannabinoid CB1 receptor and serotonin 3 receptor subunit A (5-HT3A) are co-expressed in GABA neurons in the rat telencephalon. Morales, M., Wang, S.D., Diaz-Ruiz, O., Jho, D.H. J. Comp. Neurol. (2004) [Pubmed]
  23. The neuronal distribution of cannabinoid receptor type 1 in the trigeminal ganglion of the rat. Price, T.J., Helesic, G., Parghi, D., Hargreaves, K.M., Flores, C.M. Neuroscience (2003) [Pubmed]
  24. In vivo and in vitro treatment with the synthetic cannabinoid CP55, 940 decreases the in vitro migration of macrophages in the rat: involvement of both CB1 and CB2 receptors. Sacerdote, P., Massi, P., Panerai, A.E., Parolaro, D. J. Neuroimmunol. (2000) [Pubmed]
  25. Coexistence of serotonin 3 (5-HT3) and CB1 cannabinoid receptors in interneurons of hippocampus and dentate gyrus. Morales, M., Bäckman, C. Hippocampus. (2002) [Pubmed]
  26. Cannabinoids and dopamine receptors' action on calcium current in rat neurons. Vásquez, C., Navarro-Polanco, R., Hernández, G., Ruiz, J., Guerra, D.G., Baltazar, L.M., Huerta, M., Trujillo, X. The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques. (2005) [Pubmed]
  27. The CB(1) cannabinoid receptor is coupled to the activation of c-Jun N-terminal kinase. Rueda, D., Galve-Roperh, I., Haro, A., Guzmán, M. Mol. Pharmacol. (2000) [Pubmed]
  28. 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Sugiura, T., Kondo, S., Sukagawa, A., Nakane, S., Shinoda, A., Itoh, K., Yamashita, A., Waku, K. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  29. Cannabinoid CB1 receptor protein expression in the rat choroid plexus: a possible involvement of cannabinoids in the regulation of cerebrospinal fluid. Ashton, J.C., Appleton, I., Darlington, C.L., Smith, P.F. Neurosci. Lett. (2004) [Pubmed]
  30. Cannabinoid antagonist SR-141716 inhibits endotoxic hypotension by a cardiac mechanism not involving CB1 or CB2 receptors. Bátkai, S., Pacher, P., Járai, Z., Wagner, J.A., Kunos, G. Am. J. Physiol. Heart Circ. Physiol. (2004) [Pubmed]
  31. Post-natal development of type 1 cannabinoid receptor immunoreactivity in the rat hippocampus. Morozov, Y.M., Freund, T.F. Eur. J. Neurosci. (2003) [Pubmed]
  32. Hippocampal cannabinoid-1 receptor upregulation upon endothelin-B receptor deficiency: a neuroprotective substitution effect? Unzicker, C., Erberich, H., Moldrich, G., Woldt, H., Bulla, J., Mechoulam, R., Ehrenreich, H., Sirén, A.L. Neurochem. Res. (2005) [Pubmed]
  33. Upregulation of spinal cannabinoid-1-receptors following nerve injury enhances the effects of Win 55,212-2 on neuropathic pain behaviors in rats. Lim, G., Sung, B., Ji, R.R., Mao, J. Pain (2003) [Pubmed]
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