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Psychopharmacology

, Volume 231, Issue 18, pp 3707–3718 | Cite as

Separate mechanisms for development and performance of compulsive checking in the quinpirole sensitization rat model of obsessive-compulsive disorder (OCD)

  • Mark C. Tucci
  • Anna Dvorkin-Gheva
  • Renee Sharma
  • Leena Taji
  • Paul Cheon
  • John Peel
  • Ashley Kirk
  • Henry SzechtmanEmail author
Original Investigation

Abstract

Rationale

Acute administration of serotonergic agonist, meta-chlorophenylpiperazine (mCPP), attenuates performance of compulsive checking in an animal model of obsessive-compulsive disorder (OCD). It is not known whether mCPP has a similar effect on development of compulsive checking.

Objectives

The objective of the study was to examine whether similar mechanisms mediate the development versus the performance of compulsive checking in the rat model.

Methods

Four groups of male rats (N = 14/group) were tested: two experimental groups co-injected with D2/D3 dopamine agonist quinpirole (0.25 mg/kg) and mCPP (0.625 mg/kg or 1.25 mg/kg), and two control groups, one co-injected with quinpirole and saline, the other receiving injections of saline. The time course of development of compulsive checking across injections 1 to 10 in quinpirole-treated rats was compared to rats co-injected with quinpirole and mCPP.

Results

Results showed that during the course of chronic treatment, mCPP (1.25 mg/kg) significantly attenuated performance of checking behavior. However, when these rats were retested for expression of compulsive checking (that is, with an injection of quinpirole only), their profile of compulsive checking was no different from the control rats treated throughout with quinpirole only.

Conclusions

Findings show that mCPP inhibits performance of compulsive checking but does not block quinpirole from inducing the neural substrate underlying this compulsive behavior. Hence, a separate mechanism underlies the induction of compulsive checking and the performance of it. It is suggested that development of the OCD endophenotype reflects neuroplastic changes produced by repeated dopamine D2/D3 receptor stimulation, while stimulation of serotonergic receptors mediates a negative feedback signal that shuts down the motor performance of checking.

Keywords

Compulsive checking behavior Dopamine-serotonin interaction Security motivation mCPP Quinpirole 

Notes

Acknowledgments

We thank Ms. Dawn Graham for excellent technical assistance in carrying out this study and Dr Erik Woody for advise with statistical analysis. This study was supported by operating grants to HS from the Canadian Institutes of Health Research (CIHR MOP-64424), the Natural Sciences and Engineering Research Council of Canada (RGPIN A0544), and the Ontario Mental Health Foundation, and by an Ontario Graduate Scholarship award to MCT.

Conflict of interest

The authors declare no conflict of interests.

References

  1. Albert PR, Le François B (2010) Modifying 5-HT1A receptor gene expression as a new target for antidepressant therapy. Front Neurosci 4:35PubMedCentralPubMedGoogle Scholar
  2. Alex KD, Pehek EA (2007) Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission. Pharmacol Ther 113:296–320PubMedCentralPubMedCrossRefGoogle Scholar
  3. Alkhatib AH, Dvorkin-Gheva A, Szechtman H (2013) Quinpirole and 8-OH-DPAT induce compulsive checking behavior in male rats by acting on different functional parts of an OCD neurocircuit. Behav Pharmacol 24:65–73PubMedCrossRefGoogle Scholar
  4. Amato D, Stasi MA, Borsini F, Nencini P (2008) Haloperidol both prevents and reverses quinpirole-induced nonregulatory water intake, a putative animal model of psychogenic polydipsia. Psychopharmacol (Berl) 200:157–165CrossRefGoogle Scholar
  5. Andersen SL, Greene-Colozzi EA, Sonntag KC (2010) A novel, multiple symptom model of obsessive-compulsive-like behaviors in animals. Biol Psychiatry 68:741–747PubMedCrossRefGoogle Scholar
  6. Aouizerate B, Guehl D, Cuny E, Rougier A, Bioulac B, Tignol J, Burbaud P (2004) Pathophysiology of obsessive-compulsive disorder: a necessary link between phenomenology, neuropsychology, imagery and physiology. Prog Neurobiol 72:195–221PubMedCrossRefGoogle Scholar
  7. Aouizerate B, Guehl D, Cuny E, Rougier A, Burbaud P, Tignol J, Bioulac B (2005) Updated overview of the putative role of the serotoninergic system in obsessive-compulsive disorder. Neuropsychiatr Dis Treat 1:231–43PubMedCentralPubMedGoogle Scholar
  8. Barnes NM, Sharp T (1999) A review of central 5-HT receptors and their function. Neuropharmacology 38:1083–152PubMedCrossRefGoogle Scholar
  9. Barr LC, Goodman WK, Price LH (1993) The serotonin hypothesis of obsessive compulsive disorder. Int Clin Psychopharmacol 8(Suppl 2):79–82PubMedCrossRefGoogle Scholar
  10. Baxter LR Jr (1992) Neuroimaging studies of obsessive compulsive disorder. Psychiatr Clin North Am 15:871–884PubMedGoogle Scholar
  11. Ben Pazi A, Szechtman H, Eilam D (2001) The morphogenesis of motor rituals in rats treated chronically with the dopamine agonist quinpirole. Behav Neurosci 115:1301–1317PubMedCrossRefGoogle Scholar
  12. Bloch MH, Landeros-Weisenberger A, Kelmendi B, Coric V, Bracken MB, Leckman JF (2006) A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder. Mol Psychiatry 11:622–632PubMedCrossRefGoogle Scholar
  13. Bos M, Jenck F, Martin JR, Moreau JL, Sleight AJ, Wichmann J, Widmer U (1997) Novel agonists of 5HT2C receptors. Synthesis and biological evaluation of substituted 2-(indol-1-yl)-1-methylethylamines and 2-(indeno[1,2-b]pyrrol-1-yl)-1-methylethylamines. Improved therapeutics for obsessive compulsive disorder. J Med Chem 40:2762–2769PubMedCrossRefGoogle Scholar
  14. Boulougouris V, Glennon JC, Robbins TW (2008) Dissociable effects of selective 5-HT2A and 5-HT2C receptor antagonists on serial spatial reversal learning in rats. Neuropsychopharmacology 33:2007–2019PubMedCrossRefGoogle Scholar
  15. Broocks A, Pigott TA, Hill JL, Stephanie C, Grady TA, L'Heureux F, Murphy DL (1998) Acute intravenous administration of ondansetron and m-CPP, alone and in combination, in patients with obsessive-compulsive disorder (OCD): behavioral and biological results. Psychiatry Res 79:11–20PubMedCrossRefGoogle Scholar
  16. Campbell KM, de Lecea L, Severynse DM, Caron MG, McGrath MJ, Sparber SB, Sun LY, Burton FH (1999) OCD-Like behaviors caused by a neuropotentiating transgene targeted to cortical and limbic D1+ neurons. J Neurosci 19:5044–5053PubMedGoogle Scholar
  17. Carlezon WA Jr, Nestler EJ (2002) Elevated levels of GluR1 in the midbrain: a trigger for sensitization to drugs of abuse? Trends Neurosci 25:610–615PubMedCrossRefGoogle Scholar
  18. Carpenter TL, Pazdernik TL, Levant B (2003) Differences in quinpirole-induced local cerebral glucose utilization between naive and sensitized rats. Brain Res 964:295–301PubMedCrossRefGoogle Scholar
  19. Charney DS, Goodman WK, Price LH, Woods SW, Rasmussen SA, Heninger GR (1988) Serotonin function in obsessive-compulsive disorder. A comparison of the effects of tryptophan and m-chlorophenylpiperazine in patients and healthy subjects. Arch Gen Psychiatry 45:177–85PubMedCrossRefGoogle Scholar
  20. Culver KE, Szechtman H, Levant B (2008) Altered dopamine D2-like receptor binding in rats with behavioral sensitization to quinpirole: effects of pre-treatment with Ro 41-1049. Eur J Pharmacol 592:67–72PubMedCentralPubMedCrossRefGoogle Scholar
  21. de Leeuw AS, Westenberg HG (2008) Hypersensitivity of 5-HT2 receptors in OCD patients. An increased prolactin response after a challenge with meta-chlorophenylpiperazine and pre-treatment with ritanserin and placebo. J Psychiatr Res 42:894–901PubMedCrossRefGoogle Scholar
  22. Denys D (2006) Pharmacotherapy of obsessive-compulsive disorder and obsessive-compulsive spectrum disorders. Psychiatr Clin North Am 29:553–584PubMedCrossRefGoogle Scholar
  23. Dougherty DD, Rauch SL, Jenike MA (2004) Pharmacotherapy for obsessive-compulsive disorder. J Clin Psychol 60:1195–202PubMedCrossRefGoogle Scholar
  24. Drai D, Golani I (2001) SEE: a tool for the visualization and analysis of rodent exploratory behavior. Neurosci Biobehav Rev 25:409–426PubMedCrossRefGoogle Scholar
  25. Drai D, Benjamini Y, Golani I (2000) Statistical discrimination of natural modes of motion in rat exploratory behavior. J Neurosci Methods 96:119–131PubMedCrossRefGoogle Scholar
  26. Dvorkin A, Perreault ML, Szechtman H (2006) Development and temporal organization of compulsive checking induced by repeated injections of the dopamine agonist quinpirole in an animal model of obsessive-compulsive disorder. Behav Brain Res 169:303–311PubMedCrossRefGoogle Scholar
  27. Dvorkin A, Silva C, McMurran T, Bisnaire L, Foster J, Szechtman H (2010) Features of compulsive checking behavior mediated by nucleus accumbens and orbital frontal cortex. Eur J Neurosci 32:1552–1563PubMedCrossRefGoogle Scholar
  28. Eilam D, Golani I (1989) Home base behavior of rats (Rattus norvegicus) exploring a novel environment. Behav Brain Res 34:199–211PubMedCrossRefGoogle Scholar
  29. Eilam D, Szechtman H (2005) Psychostimulant-induced behavior as an animal model of obsessive-compulsive disorder: an ethological approach to the form of compulsive rituals. CNS Spectr 10:191–202PubMedGoogle Scholar
  30. Einat H, Szechtman H (1995) Perseveration without hyperlocomotion in a spontaneous alternation task in rats sensitized to the dopamine agonist quinpirole. Physiol Behav 57:55–9PubMedCrossRefGoogle Scholar
  31. Fineberg NA, Gale TM, Sivakumaran T (2006) A review of antipsychotics in the treatment of obsessive compulsive disorder. J Psychopharmacol 20:97–103PubMedCrossRefGoogle Scholar
  32. Fink KB, Göthert M (2007) 5-HT receptor regulation of neurotransmitter release. Pharmacol Rev 59:360–417PubMedCrossRefGoogle Scholar
  33. Flaisher-Grinberg S, Klavir O, Joel D (2008) The role of 5-HT2A and 5-HT2C receptors in the signal attenuation rat model of obsessive-compulsive disorder. Int J Neuropsychopharmacol 11:811–25PubMedGoogle Scholar
  34. Gatch MB (2003) Discriminative stimulus effects of m-chlorophenylpiperazine as a model of the role of serotonin receptors in anxiety. Life Sci 73:1347–1367PubMedCrossRefGoogle Scholar
  35. Golani I, Benjamini Y, Eilam D (1993) Stopping behavior: constraints on exploration in rats (Rattus norvegicus). Behav Brain Res 53:21–33PubMedCrossRefGoogle Scholar
  36. Goodman WK, McDougle CJ, Price LH, Riddle MA, Pauls DL, Leckman JF (1990) Beyond the serotonin hypothesis: a role for dopamine in some forms of obsessive compulsive disorder? J Clin Psychiatry 51(Suppl):36–43, discussion 55-58PubMedGoogle Scholar
  37. Goodman WK, McDougle CJ, Price LH, Barr LC, Hills OF, Caplik JF, Charney DS, Heninger GR (1995) m-Chlorophenylpiperazine in patients with obsessive-compulsive disorder: Absence of symptom exacerbation. Biol Psychiatry 38:138–149PubMedCrossRefGoogle Scholar
  38. Graybiel AM, Rauch SL (2000) Toward a neurobiology of obsessive-compulsive disorder. Neuron 28:343–347PubMedCrossRefGoogle Scholar
  39. Greene-Schloesser DM, Van der Zee EA, Sheppard DK, Castillo MR, Gregg KA, Burrow T, Foltz H, Slater M, Bult-Ito A (2011) Predictive validity of a non-induced mouse model of compulsive-like behavior. Behav Brain Res 221:55–62PubMedCentralPubMedCrossRefGoogle Scholar
  40. Gross-Isseroff R, Cohen R, Sasson Y, Voet H, Zohar J (2004) Serotonergic dissection of obsessive compulsive symptoms: a challenge study with m-chlorophenylpiperazine and sumatriptan. Neuropsychobiology 50:200–5PubMedCrossRefGoogle Scholar
  41. Hayes DJ, Greenshaw AJ (2011) 5-HT receptors and reward-related behaviour: a review. Neurosci Biobehav Rev 35:1419–1449PubMedCrossRefGoogle Scholar
  42. Hen I, Sakov A, Kafkafi N, Golani I, Benjamini Y (2004) The dynamics of spatial behavior: how can robust smoothing techniques help? J Neurosci Methods 133:161–172PubMedCrossRefGoogle Scholar
  43. Hikosaka O, Nakamura K, Sakai K, Nakahara H (2002) Central mechanisms of motor skill learning. Curr Opin Neurobiol 12:217–222PubMedCrossRefGoogle Scholar
  44. Hinds AL, Woody EZ, Van Ameringen M, Schmidt LA, Szechtman H (2012) When too much is not enough: obsessive-compulsive disorder as a pathology of stopping, rather than starting. PLoS ONE 7:e30586PubMedCentralPubMedCrossRefGoogle Scholar
  45. Ho Pian KL, Westenberg HG, den Boer JA, de Bruin WI, van Rijk PP (1998) Effects of meta-chlorophenylpiperazine on cerebral blood flow in obsessive-compulsive disorder and controls. Biol Psychiatry 44:367–70PubMedCrossRefGoogle Scholar
  46. Hoffman KL, Rueda Morales RI (2012) D1 and D2 dopamine receptor antagonists decrease behavioral bout duration, without altering the bout's repeated behavioral components, in a naturalistic model of repetitive and compulsive behavior. Behav Brain Res 230:1–10PubMedCrossRefGoogle Scholar
  47. Hollander E, DeCaria C, Gully R, Nitescu A, Suckow RF, Gorman JM, Klein DF, Liebowitz MR (1991) Effects of chronic fluoxetine treatment on behavioral and neuroendocrine responses to meta-chlorophenylpiperazine in obsessive-compulsive disorder. Psychiatry Res 36:1–17PubMedCrossRefGoogle Scholar
  48. Huey ED, Zahn R, Krueger F, Moll J, Kapogiannis D, Wassermann EM, Grafman J (2008) A psychological and neuroanatomical model of obsessive-compulsive disorder. J Neuropsychiatry Clin Neurosci 20:390–408PubMedCrossRefGoogle Scholar
  49. Insel TR (1992) Neurobiology of obsessive compulsive disorder: a review. Int Clin Psychopharmacol 7(Suppl 1):31–33, 31-33PubMedCrossRefGoogle Scholar
  50. Insel TR, Mueller EA, Alterman I, Linnoila M, Murphy DL (1985) Obsessive-compulsive disorder and serotonin: is there a connection? Biol Psychiatry 20:1174–1188PubMedCrossRefGoogle Scholar
  51. Jimenez-Gomez C, Osentoski A, Woods JH (2011) Pharmacological evaluation of the adequacy of marble burying as an animal model of compulsion and/or anxiety. Behav Pharmacol 22:711–713PubMedCrossRefGoogle Scholar
  52. Joel D (2006) The signal attenuation rat model of obsessive-compulsive disorder: a review. Psychopharmacol (Berl) 186:487–503CrossRefGoogle Scholar
  53. Joel D, Avisar A, Doljansky J (2001) Enhancement of excessive lever-pressing after post-training signal attenuation in rats by repeated administration of the D1 antagonist SCH 23390 or the D2 agonist quinpirole, but not the D1 agonist SKF 38393 or the D2 antagonist haloperidol. Behav Neurosci 115:1291–1300PubMedCrossRefGoogle Scholar
  54. Khanna S, John JP, Lakshmi Reddy P (2001) Neuroendocrine and behavioral responses to mCPP in obsessive-compulsive disorder. Psychoneuroendocrinology 26:209–223PubMedCrossRefGoogle Scholar
  55. Kontis D, Tsaltas E, Boulougouris V, Papakosta VM, Kalogerakou S, Papadopoulos S, Papadimitriou G (2008) 5-HT2A and 5-HT2C receptor involvement in the acute effects of mCPP and fluoxetine on persistence behaviour. Int J Neuropsychopharmacol 11:282–282Google Scholar
  56. Korff S, Stein DJ, Harvey BH (2008) Stereotypic behaviour in the deer mouse: pharmacological validation and relevance for obsessive compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry 32:348–355PubMedCrossRefGoogle Scholar
  57. Kurylo DD (2004) Effects of quinpirole on operant conditioning: perseveration of behavioral components. Behav Brain Res 155:117–124PubMedCrossRefGoogle Scholar
  58. Martin JR, Bos M, Jenck F, Moreau J, Mutel V, Sleight AJ, Wichmann J, Andrews JS, Berendsen HH, Broekkamp CL, Ruigt GS, Kohler C, Delft AM (1998) 5-HT2C receptor agonists: pharmacological characteristics and therapeutic potential. J Pharmacol Exp Ther 286:913–924PubMedGoogle Scholar
  59. Modell JG, Mountz JM, Curtis GC, Greden JF (1989) Neurophysiologic dysfunction in basal ganglia/limbic striatal and thalamocortical circuits as a pathogenetic mechanism of obsessive-compulsive disorder. J Neuropsychiatry Clin Neurosci 1:27–36PubMedGoogle Scholar
  60. Murphy DL, Zohar J, Benkelfat C, Pato MT, Pigott TA, Insel TR (1989) Obsessive-compulsive disorder as a 5-HT subsystem-related behavioural disorder. Br J Psychiatry Suppl 15–24Google Scholar
  61. Noldus LP, Spink AJ, Tegelenbosch RA (2001) EthoVision: a versatile video tracking system for automation of behavioral experiments. Behav Res Methods Instrum Comput 33:398–414PubMedCrossRefGoogle Scholar
  62. Papakosta VM, Kalogerakou S, Kontis D, Anyfandi E, Theochari E, Boulougouris V, Papadopoulos S, Panagis G, Tsaltas E (2013) 5-HT2C receptor involvement in the control of persistence in the reinforced spatial alternation animal model of obsessive-compulsive disorder. Behav Brain Res 243:176–83PubMedCrossRefGoogle Scholar
  63. Perreault ML, Graham D, Bisnaire L, Simms J, Hayton S, Szechtman H (2005) Kappa-opioid agonist U69593 potentiates locomotor sensitization to the D2/D3 agonist quinpirole: pre- and postsynaptic mechanisms. Neuropsychopharmacology 31:1967–1981PubMedCrossRefGoogle Scholar
  64. Perreault ML, Seeman P, Szechtman H (2007) Kappa-opioid receptor stimulation quickens pathogenesis of compulsive checking in the quinpirole Sensitization model of obsessive-compulsive disorder (OCD). Behav Neurosci 121:976–991PubMedCrossRefGoogle Scholar
  65. Pigott TA, Hill JL, Grady TA, L'Heureux F, Bernstein S, Rubenstein CS, Murphy DL (1993) A comparison of the behavioral effects of oral versus intravenous mCPP administration in OCD patients and the effect of metergoline prior to i.v. mCPP. Biol Psychiatry 33:3–14PubMedCrossRefGoogle Scholar
  66. Pitman RK (1989) Animal models of compulsive behavior. Biol Psychiatry 26:189–198PubMedCrossRefGoogle Scholar
  67. Rajkumar R, Pandey DK, Mahesh R, Radha R (2009) 1-(m-Chlorophenyl)piperazine induces depressogenic-like behaviour in rodents by stimulating the neuronal 5-HT2A receptors: proposal of a modified rodent antidepressant assay. Eur J Pharmacol 608:32–41PubMedCrossRefGoogle Scholar
  68. Richards TL, Pazdernik TL, Levant B (2005) Altered quinpirole-induced local cerebral glucose utilization in anterior cortical regions in rats after sensitization to quinpirole. Brain Res 1042:53–61PubMedCrossRefGoogle Scholar
  69. Saxena S, Bota RG, Brody AL (2001) Brain-behavior relationships in obsessive-compulsive disorder. Semin Clin Neuropsychiatry 6:82–101PubMedCrossRefGoogle Scholar
  70. Schepisi C, De Carolis L, Nencini P (2013) Effects of the 5HT2C antagonist SB242084 on the pramipexole-induced potentiation of water contrafreeloading, a putative animal model of compulsive behavior. Psychopharmacol (Berl) 227:55–66CrossRefGoogle Scholar
  71. Schilman EA, Klavir O, Winter C, Sohr R, Joel D (2010) The role of the striatum in compulsive behavior in intact and orbitofrontal-cortex-lesioned rats: possible involvement of the serotonergic system. Neuropsychopharmacology 35:1026–1039PubMedCentralPubMedCrossRefGoogle Scholar
  72. Seeman P, Schwarz J, Chen JF, Szechtman H, Perreault M, McKnight GS, Roder JC, Quirion R, Boksa P, Srivastava LK, Yanai K, Weinshenker D, Sumiyoshi T (2006) Psychosis pathways converge via D2high dopamine receptors. Synapse 60:319–46PubMedCrossRefGoogle Scholar
  73. Sesia T, Bizup B, Grace AA (2013) Evaluation of animal models of obsessive-compulsive disorder: correlation with phasic dopamine neuron activity. International Journal of Neuropsychopharmacology: 1-13Google Scholar
  74. Shanahan NA, Velez LP, Masten VL, Dulawa SC (2011) Essential role for orbitofrontal serotonin 1B receptors in obsessive-compulsive disorder-like behavior and serotonin reuptake inhibitor response in mice. Biol Psychiatry 70:1039–48PubMedCentralPubMedCrossRefGoogle Scholar
  75. Spink AJ, Tegelenbosch RA, Buma MO, Noldus LP (2001) The EthoVision video tracking system—a tool for behavioral phenotyping of transgenic mice. Physiol Behav 73:731–744PubMedCrossRefGoogle Scholar
  76. Stein DJ (2002) Obsessive-compulsive disorder. Lancet 360:397–405PubMedCrossRefGoogle Scholar
  77. Sullivan RM, Talangbayan H, Einat H, Szechtman H (1998) Effects of quinpirole on central dopamine systems in sensitized and non-sensitized rats. Neuroscience 83:781–9PubMedCrossRefGoogle Scholar
  78. Szechtman H, Eilam D (2005) Psychiatric models. In: Whishaw IQ, Kolb B (eds) The behavior of the laboratory rat: a handbook with tests. Oxford University Press, New York, pp 462–474Google Scholar
  79. Szechtman H, Woody E (2004) Obsessive-compulsive disorder as a disturbance of security motivation. Psychol Rev 111:111–127PubMedCrossRefGoogle Scholar
  80. Szechtman H, Dai H, Mustafa S, Einat H, Sullivan RM (1994a) Effects of dose and interdose interval on locomotor sensitization to the dopamine agonist quinpirole. Pharmacol Biochem Behav 48:921–928PubMedCrossRefGoogle Scholar
  81. Szechtman H, Talangbayan H, Canaran G, Dai H, Eilam D (1994b) Dynamics of behavioral sensitization induced by the dopamine agonist quinpirole and a proposed central energy control mechanism [published erratum appears in Psychopharmacology (Berl) 1994 Sep;116(1):124]. Psychopharmacol (Berl) 115:95–104CrossRefGoogle Scholar
  82. Szechtman H, Sulis W, Eilam D (1998) Quinpirole induces compulsive checking behavior in rats: a potential animal model of obsessive-compulsive disorder (OCD). Behav Neurosci 112:1475–1485PubMedCrossRefGoogle Scholar
  83. Szechtman H, Shivji S, Woody EZ (2013) Pathophysiology of obsessive-compulsive disorder: insights from normal function and neurotoxic effects of drugs, infection and brain injury. In: Kostrzewa RM (ed) Handbook of neurotoxicity. Springer London, LimitedGoogle Scholar
  84. Szumlinski KK, Allan M, Talangbayan H, Tracey A, Szechtman H (1997) Locomotor sensitization to quinpirole: environment-modulated increase in efficacy and context-dependent increase in potency. Psychopharmacoly (Berl) 134:193–200Google Scholar
  85. Tolkamp BJ, Kyriazakis I (1999) To split behaviour into bouts, log-transform the intervals. Anim Behav 57:807–817PubMedCrossRefGoogle Scholar
  86. Tolkamp BJ, Allcroft DJ, Austin EJ, Nielsen BL, Kyriazakis I (1998) Satiety splits feeding behaviour into bouts. J Theor Biol 194:235–250PubMedCrossRefGoogle Scholar
  87. Tucci MC, Dvorkin-Gheva A, Graham D, Amodeo S, Cheon P, Kirk A, Peel J, Taji L, Szechtman H (2013) Effects of the serotonergic agonist mCPP on male rats in the quinpirole sensitization model of obsessive-compulsive disorder (OCD). Psychopharmacol (Berl) 227:277–285CrossRefGoogle Scholar
  88. Vermeire S, Audenaert K, De Meester R, Vandermeulen E, Waelbers T, De Spiegeleer B, Eersels J, Dobbeleir A, Peremans K (2012) Serotonin 2A receptor, serotonin transporter and dopamine transporter alterations in dogs with compulsive behaviour as a promising model for human obsessive-compulsive disorder. Psychiatry Res Neuroimaging 201:78–87CrossRefGoogle Scholar
  89. Vezina P, Stewart J (1990) Amphetamine administered to the ventral tegmental area but not to the nucleus accumbens sensitizes rats to systemic morphine: lack of conditioned effects. Brain Res 516:99–106PubMedCrossRefGoogle Scholar
  90. Westenberg HG, Fineberg NA, Denys D (2007) Neurobiology of obsessive-compulsive disorder: serotonin and beyond. CNS Spectr 12:14–27PubMedGoogle Scholar
  91. Wise S, Rapoport JL (1989) Obsessive compulsive disorder—is it a basal ganglia dysfunction? In: Rapoport J (ed) Obsessive compulsive disorder in children and adolescence. American Psychiatric Press, Washington, DC, pp 327–344Google Scholar
  92. Woody EZ, Szechtman H (2005) Motivation, time course, and heterogeneity in obsessive-compulsive disorder: response to Taylor, McKay, and Abramowitz (2005). Psychol Rev 112:658–661CrossRefGoogle Scholar
  93. Woody EZ, Szechtman H (2011) Adaptation to potential threat: the evolution, neurobiology, and psychopathology of the security motivation system. Neurosci Biobehav Rev 35:1019–1033PubMedCrossRefGoogle Scholar
  94. Yadin E, Friedman E, Bridger WH (1991) Spontaneous alternation behavior: an animal model for obsessive-compulsive disorder? Pharmacol Biochem Behav 40:311–315PubMedCrossRefGoogle Scholar
  95. Zohar J, Mueller EA, Insel TR, Zohar-Kadouch RC, Murphy DL (1987) Serotonergic responsivity in obsessive-compulsive disorder. Comparison of patients and healthy controls. Arch Gen Psychiatry 44:946–51PubMedCrossRefGoogle Scholar
  96. Zohar J, Chopra M, Sasson Y, Amiaz R, Amital D (2000) Obsessive compulsive disorder: serotonin and beyond. World J Biol Psychiatry 1:92–100PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Mark C. Tucci
    • 1
  • Anna Dvorkin-Gheva
    • 1
  • Renee Sharma
    • 1
  • Leena Taji
    • 1
  • Paul Cheon
    • 1
  • John Peel
    • 1
  • Ashley Kirk
    • 1
  • Henry Szechtman
    • 1
    Email author
  1. 1.Department of Psychiatry and Behavioural NeurosciencesMcMaster UniversityHamiltonCanada

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