Psychopharmacology

, Volume 226, Issue 3, pp 579–587 | Cite as

Effects of glutamate NMDA and TRPV1 receptor antagonists on the biphasic responses to anandamide injected into the dorsolateral periaqueductal grey of Wistar rats

  • Manoela V. Fogaça
  • Felipe V. Gomes
  • Fabrício A. Moreira
  • Francisco S. Guimarães
  • Daniele C. Aguiar
Original Investigation

Abstract

Rationale

The endocannabinoid and endovanniloid anandamide (AEA) exerts biphasic effects when injected into the dorsolateral periaqueductal grey (dlPAG) in rats submitted to threatening situations. Whereas lower doses of AEA induce anxiolytic-like effects by activating cannabinoid CB1 receptors, no effects are observed with higher doses, possibly due to the simultaneous activation of transient receptor potential vanilloid type 1 (TRPV1) receptors. This activation would facilitate glutamatergic neurotransmission.

Objective

Considering that the blockade of TRPV1 or NMDA receptors in the dlPAG induces anxiolytic-like effects, we tested the hypothesis that facilitation of glutamate transmission through TRPV1 is responsible for the lack of anxiolytic-like effect observed with high AEA doses.

Methods

Male Wistar rats with a unilateral cannula aimed at the dlPAG received injections of an ineffective dose of AP7 (an NMDA antagonist, 1 nmol) or capsazepine (CPZ, a TRPV1 antagonist, 10 nmol), followed by a high dose of AEA (50 and 200 pmol) and were exposed to the elevated plus maze (EPM) or the Vogel conflict test (VCT).

Results

AP7, CPZ, or AEA did not induce any significant effects when administered alone. However, AP7 or CPZ prior to AEA significantly increased the percentage of entries and time spent in the open arms of EPM and the number of punished licks in the VCT suggesting an anxiolytic-like effect.

Conclusions

These results suggest that the lack of anxiolytic-like effect of higher AEA doses is due to facilitation of glutamate release in the dlPAG, probably via activation of TRPV1 receptors in this structure.

Keywords

Glutamate Endovanilloids Anxiety Defensive behavior 

Notes

Acknowledgments

This research was supported by grants from CAPES, CNPq, FAPESP, and FAPEMIG (APQ-01883-10). We thank J.C. de Aguiar and E.T. Gomes for the excellent technical support.

References

  1. Aguiar DC, Guimaraes FS (2009) Blockade of NMDA receptors and nitric oxide synthesis in the dorsolateral periaqueductal gray attenuates behavioral and cellular responses of rats exposed to a live predator. J Neurosci Res 87:2418–2429PubMedCrossRefGoogle Scholar
  2. Aguiar DC, Moreira FA, Guimaraes FS (2006) Flight reactions induced by injection of glutamate N-methyl-d-aspartate receptor agonist into the rat dorsolateral periaqueductal gray are not dependent on endogenous nitric oxide. Pharmacol Biochem Behav 83:296–301PubMedCrossRefGoogle Scholar
  3. Aguiar DC, Terzian AL, Guimaraes FS, Moreira FA (2009) Anxiolytic-like effects induced by blockade of transient receptor potential vanilloid type 1 (TRPV1) channels in the medial prefrontal cortex of rats. Psychopharmacol (Berl) 205:217–225CrossRefGoogle Scholar
  4. Bandler R, Keay KA, Floyd N, Price J (2000) Central circuits mediating patterned autonomic activity during active vs. passive emotional coping. Brain Res Bull 53:95–104PubMedCrossRefGoogle Scholar
  5. Bittencourt AS, Carobrez AP, Zamprogno LP, Tufik S, Schenberg LC (2004) Organization of single components of defensive behaviors within distinct columns of periaqueductal gray matter of the rat: role of N-methyl-d-aspartic acid glutamate receptors. Neuroscience 125:71–89PubMedCrossRefGoogle Scholar
  6. Campos AC, Guimaraes FS (2008) Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats. Psychopharmacol (Berl) 199:223–230CrossRefGoogle Scholar
  7. Carrive P (1993) The periaqueductal gray and defensive behavior: functional representation and neuronal organization. Behav Brain Res 58:27–47PubMedCrossRefGoogle Scholar
  8. Casarotto PC, Terzian AL, Aguiar DC, Zangrossi H, Guimaraes FS, Wotjak CT, Moreira FA (2012) Opposing roles for cannabinoid receptor type-1 (CB(1)) and transient receptor potential vanilloid type-1 channel (TRPV1) on the modulation of panic-like responses in rats. Neuropsychopharmacology 37:478–486PubMedCrossRefGoogle Scholar
  9. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824PubMedCrossRefGoogle Scholar
  10. Cavanaugh DJ, Chesler AT, Jackson AC, Sigal YM, Yamanaka H, Grant R, O'Donnell D, Nicoll RA, Shah NM, Julius D, Basbaum AI (2011) Trpv1 reporter mice reveal highly restricted brain distribution and functional expression in arteriolar smooth muscle cells. J Neurosci 31:5067–5077PubMedCrossRefGoogle Scholar
  11. Clapham DE, Julius D, Montell C, Schultz G (2005) International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels. Pharmacol Rev 57:427–450PubMedCrossRefGoogle Scholar
  12. Cristino L, de Petrocellis L, Pryce G, Baker D, Guglielmotti V, Di Marzo V (2006) Immunohistochemical localization of cannabinoid type 1 and vanilloid transient receptor potential vanilloid type 1 receptors in the mouse brain. Neuroscience 139:1405–1415PubMedCrossRefGoogle Scholar
  13. Di Marzo V, Bisogno T, De Petrocellis L (2001) Anandamide: some like it hot. Trends Pharmacol Sci 22:346–349PubMedCrossRefGoogle Scholar
  14. File SE (1992) Behavioural detection of anxiolytic action. In: Elliot JM, Heal DJ, Marsden CA (eds) Experimental approaches to anxiety and depression. Wiley, New York, pp 25–44Google Scholar
  15. Finn DP, Jhaveri MD, Beckett SR, Roe CH, Kendall DA, Marsden CA, Chapman V (2003) Effects of direct periaqueductal grey administration of a cannabinoid receptor agonist on nociceptive and aversive responses in rats. Neuropharmacology 45:594–604PubMedCrossRefGoogle Scholar
  16. Fogaca MV, Aguiar DC, Moreira FA, Guimaraes FS (2012) The endocannabinoid and endovanilloid systems interact in the rat prelimbic medial prefrontal cortex to control anxiety-like behavior. Neuropharmacology 63:202–210PubMedCrossRefGoogle Scholar
  17. Geller I, Seifter J (1960) The effects of meprobamate, barbiturate, damphetamine and promazine on experimentally induced conflict in the rat. Psychopharmacologia 1:482–492CrossRefGoogle Scholar
  18. Guimaraes FS, Carobrez AP, De Aguiar JC, Graeff FG (1991) Anxiolytic effect in the elevated plus-maze of the NMDA receptor antagonist AP7 microinjected into the dorsal periaqueductal grey. Psychopharmacol (Berl) 103:91–94CrossRefGoogle Scholar
  19. Guimaraes FS, Beijamini V, Moreira FA, Aguiar DC, de Lucca AC (2005) Role of nitric oxide in brain regions related to defensive reactions. Neurosci Biobehav Rev 29:1313–1322PubMedCrossRefGoogle Scholar
  20. Jin YH, Takemura M, Furuyama A, Yonehara N (2012) Peripheral glutamate receptors are required for hyperalgesia induced by capsaicin. Pain Res Treat 2012:915706PubMedGoogle Scholar
  21. Kawahara H, Drew G, Christie M, Vaughan C (2011) Inhibition of fatty acid amide hydrolase unmasks CB(1) receptor and TRPV1 channel-mediated modulation of glutamatergic synaptic transmission in midbrain periaqueductal grey. Br J Pharmacol 163:1214–1222PubMedCrossRefGoogle Scholar
  22. Lisboa SF, Guimaraes FS (2012) Differential role of CB1 and TRPV1 receptors on anandamide modulation of defensive responses induced by nitric oxide in the dorsolateral periaqueductal gray. Neuropharmacology 62:2455–2462PubMedCrossRefGoogle Scholar
  23. Lisboa SF, Resstel LB, Aguiar DC, Guimaraes FS (2008) Activation of cannabinoid CB1 receptors in the dorsolateral periaqueductal gray induces anxiolytic effects in rats submitted to the Vogel conflict test. Eur J Pharmacol 593:73–78PubMedCrossRefGoogle Scholar
  24. Maione S, Bisogno T, de Novellis V, Palazzo E, Cristino L, Valenti M, Petrosino S, Guglielmotti V, Rossi F, Di Marzo V (2006) Elevation of endocannabinoid levels in the ventrolateral periaqueductal grey through inhibition of fatty acid amide hydrolase affects descending nociceptive pathways via both cannabinoid receptor type 1 and transient receptor potential vanilloid type-1 receptors. J Pharmacol Exp Ther 316:969–982PubMedCrossRefGoogle Scholar
  25. Maione S, Cristino L, Migliozzi AL, Georgiou AL, Starowicz K, Salt TE, Di Marzo V (2009) TRPV1 channels control synaptic plasticity in the developing superior colliculus. J Physiol 587:2521–2535PubMedCrossRefGoogle Scholar
  26. Marinelli S, Vaughan CW, Christie MJ, Connor M (2002) Capsaicin activation of glutamatergic synaptic transmission in the rat locus coeruleus in vitro. J Physiol 543:531–540PubMedCrossRefGoogle Scholar
  27. Marinelli S, Di Marzo V, Berretta N, Matias I, Maccarrone M, Bernardi G, Mercuri NB (2003) Presynaptic facilitation of glutamatergic synapses to dopaminergic neurons of the rat substantia nigra by endogenous stimulation of vanilloid receptors. J Neurosci 23:3136–3144PubMedGoogle Scholar
  28. Marsch R, Foeller E, Rammes G, Bunck M, Kossl M, Holsboer F, Zieglgansberger W, Landgraf R, Lutz B, Wotjak CT (2007) Reduced anxiety, conditioned fear, and hippocampal long-term potentiation in transient receptor potential vanilloid type 1 receptor-deficient mice. J Neurosci 27:832–839PubMedCrossRefGoogle Scholar
  29. Matheus MG, Guimaraes FS (1997) Antagonism of non-NMDA receptors in the dorsal periaqueductal grey induces anxiolytic effect in the elevated plus maze. Psychopharmacol (Berl) 132:14–18CrossRefGoogle Scholar
  30. McGaraughty S, Chu KL, Bitner RS, Martino B, El Kouhen R, Han P, Nikkel AL, Burgard EC, Faltynek CR, Jarvis MF (2003) Capsaicin infused into the PAG affects rat tail flick responses to noxious heat and alters neuronal firing in the RVM. J Neurophysiol 90:2702–2710PubMedCrossRefGoogle Scholar
  31. McGregor IS, Hargreaves GA, Apfelbach R, Hunt GE (2004) Neural correlates of cat odor-induced anxiety in rats: region-specific effects of the benzodiazepine midazolam. J Neurosci 24:4134–4144PubMedCrossRefGoogle Scholar
  32. Molchanov ML, Guimaraes FS (2002) Anxiolytic-like effects of AP7 injected into the dorsolateral or ventrolateral columns of the periaqueductal gray of rats. Psychopharmacol (Berl) 160:30–38CrossRefGoogle Scholar
  33. Moreira FA, Aguiar DC, Guimaraes FS (2006) Anxiolytic-like effect of cannabidiol in the rat Vogel conflict test. Prog Neuropsychopharmacol Biol Psychiatry 30:1466–1471PubMedCrossRefGoogle Scholar
  34. Moreira FA, Aguiar DC, Guimaraes FS (2007) Anxiolytic-like effect of cannabinoids injected into the rat dorsolateral periaqueductal gray. Neuropharmacology 52:958–965PubMedCrossRefGoogle Scholar
  35. Moreira FA, Aguiar DC, Terzian AL, Guimaraes FS, Wotjak CT (2012) Cannabinoid type 1 receptors and transient receptor potential vanilloid type 1 channels in fear and anxiety-two sides of one coin? Neuroscience 204:186–192PubMedCrossRefGoogle Scholar
  36. Palazzo E, Marabese I, de Novellis V, Oliva P, Rossi F, Berrino L, Maione S (2001) Metabotropic and NMDA glutamate receptors participate in the cannabinoid-induced antinociception. Neuropharmacology 40:319–326PubMedCrossRefGoogle Scholar
  37. Palazzo E, de Novellis V, Marabese I, Cuomo D, Rossi F, Berrino L, Rossi F, Maione S (2002) Interaction between vanilloid and glutamate receptors in the central modulation of nociception. Eur J Pharmacol 439:69–75PubMedCrossRefGoogle Scholar
  38. Palazzos E, de Novellis V, Marabese I, Rossi F, Maione S (2006) Metabotropic glutamate and cannabinoid receptor crosstalk in periaqueductal grey pain processing. Curr Neuropharmacol 4:225–231PubMedCrossRefGoogle Scholar
  39. Paxinos G, Watson C (1997) The rat brain in stereotaxic coordinates, 3rd edn. Academic Press, New YorkGoogle Scholar
  40. Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates, 6th edn. Academic Press/Elsevier, LondonGoogle Scholar
  41. Pellow S, File SE (1986) Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat. Pharmacol Biochem Behav 24:525–529PubMedCrossRefGoogle Scholar
  42. Pertwee RG (2006) The pharmacology of cannabinoid receptors and their ligands: an overview. Int J Obes (Lond) 30(Suppl 1):S13–S18CrossRefGoogle Scholar
  43. Ross RA (2003) Anandamide and vanilloid TRPV1 receptors. Br J Pharmacol 140:790–801PubMedCrossRefGoogle Scholar
  44. Rubino T, Realini N, Castiglioni C, Guidali C, Vigano D, Marras E, Petrosino S, Perletti G, Maccarrone M, Di Marzo V, Parolaro D (2008) Role in anxiety behavior of the endocannabinoid system in the prefrontal cortex. Cereb Cortex 18:1292–1301PubMedCrossRefGoogle Scholar
  45. Santos CJ, Stern CA, Bertoglio LJ (2008) Attenuation of anxiety-related behaviour after the antagonism of transient receptor potential vanilloid type 1 channels in the rat ventral hippocampus. Behav Pharmacol 19:357–360PubMedCrossRefGoogle Scholar
  46. Smart D, Jerman JC (2000) Anandamide: an endogenous activator of the vanilloid receptor. Trends Pharmacol Sci 21:134PubMedCrossRefGoogle Scholar
  47. Starowicz K, Maione S, Cristino L, Palazzo E, Marabese I, Rossi F, de Novellis V, Di Marzo V (2007) Tonic endovanilloid facilitation of glutamate release in brainstem descending antinociceptive pathways. J Neurosci 27:13739–13749PubMedCrossRefGoogle Scholar
  48. Terzian AL, Aguiar DC, Guimaraes FS, Moreira FA (2009) Modulation of anxiety-like behaviour by Transient Receptor Potential Vanilloid Type 1 (TRPV1) channels located in the dorsolateral periaqueductal gray. Eur Neuropsychopharmacol 19:188–195PubMedCrossRefGoogle Scholar
  49. Toth A, Boczan J, Kedei N, Lizanecz E, Bagi Z, Papp Z, Edes I, Csiba L, Blumberg PM (2005) Expression and distribution of vanilloid receptor 1 (TRPV1) in the adult rat brain. Brain Res Mol Brain Res 135:162–168PubMedCrossRefGoogle Scholar
  50. Urban L, Dray A (1992) Synaptic activation of dorsal horn neurons by selective C-fibre excitation with capsaicin in the mouse spinal cord in vitro. Neuroscience 47:693–702PubMedCrossRefGoogle Scholar
  51. Urban L, Willetts J, Randic M, Papka RE (1985) The acute and chronic effects of capsaicin on slow excitatory transmission in rat dorsal horn. Brain Res 330:390–396PubMedCrossRefGoogle Scholar
  52. Vaughan CW, Connor M, Bagley EE, Christie MJ (2000) Actions of cannabinoids on membrane properties and synaptic transmission in rat periaqueductal gray neurons in vitro. Mol Pharmacol 57:288–295PubMedGoogle Scholar
  53. Viveros MP, Marco EM, Llorente R, Lopez-Gallardo M (2007) Endocannabinoid system and synaptic plasticity: implications for emotional responses. Neural Plast 2007:52908PubMedCrossRefGoogle Scholar
  54. Walker JM, Huang SM, Strangman NM, Tsou K, Sanudo-Pena MC (1999) Pain modulation by release of the endogenous cannabinoid anandamide. Proc Natl Acad Sci USA 96:12198–12203PubMedCrossRefGoogle Scholar
  55. Xing J, Li J (2007) TRPV1 receptor mediates glutamatergic synaptic input to dorsolateral periaqueductal gray (dl-PAG) neurons. J Neurophysiol 97:503–511PubMedCrossRefGoogle Scholar
  56. You IJ, Jung YH, Kim MJ, Kwon SH, Hong SI, Lee SY, Jang CG (2012) Alterations in the emotional and memory behavioral phenotypes of transient receptor potential vanilloid type 1-deficient mice are mediated by changes in expression of 5-HT(1A), GABA(A), and NMDA receptors. Neuropharmacology 62:1034–1043PubMedCrossRefGoogle Scholar
  57. Zhou HY, Chen SR, Chen H, Pan HL (2009) The glutamatergic nature of TRPV1-expressing neurons in the spinal dorsal horn. J Neurochem 108:305–318PubMedCrossRefGoogle Scholar
  58. Zygmunt PM, Julius I, Di Marzo I, Hogestatt ED (2000) Anandamide—the other side of the coin. Trends Pharmacol Sci 21:43–44PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Manoela V. Fogaça
    • 1
    • 3
  • Felipe V. Gomes
    • 1
    • 3
  • Fabrício A. Moreira
    • 2
  • Francisco S. Guimarães
    • 1
    • 3
  • Daniele C. Aguiar
    • 2
  1. 1.Department of Pharmacology, School of Medicine of Ribeirão PretoUniversity of São PauloRibeirão PretoBrazil
  2. 2.Department of Pharmacology, Institute of Biological SciencesUniversidade Federal de Minas GeraisBelo HorizonteBrazil
  3. 3.Center for Interdisciplinary Research on Applied Neurosciences (NAPNA)University of São PauloSão PauloBrazil

Personalised recommendations