Professor, Psychiatry & Behavioural Neurosciences
Associate Member, Psychology
Associate Member, Biology
B.Sc., McGill University; Ph.D., University of Pittsburgh
Tel: 905-525-9140 ext. 22201
Chronic exposure to psychostimulant drugs has two behavioral effects
that are of particular interest. The first one is a progressive
increase in the drug response with chronic treatment, a phenomenon
termed behavioral sensitization. The phenomenon is puzzling from
a mechanistic point of view because it is not known why chronic
drug exposure would result in sensitization, rather than in the
expected tolerance. Sensitization is also puzzling from a functional
perspective because it may be linked to the emergence of psychosis,
mania, post-traumatic stress disorder, panic disorder, and addiction.
Behavioral analysis in my lab has characterized sensitization induced
by the dopamine agonist quinpirole as a process of build-up and
strengthening of performance, thus casting sensitization as a normal
biological process of enhancing motor capacity. We are now investigating
the hypothesis that increased motor vigour under the drug reflects
enhanced activity of dopaminergic neurons controlling energy expenditure.
The second interesting effect of chronic exposure to psychostimulant
drugs is the resultant transformation in the organization of activity:
under quinpirole, for instance, behavior is strikingly organized,
despite a marked increase in hyperactivity. In a large open field,
sensitized rats move repeatedly along paths that are rigid and restricted
to only a portion of the environment. As they travel, they tend
to stop in specific places along their route and display fixed motor
acts. Their behavior appears as if it were a compulsive motor ritual.
Together with Dr David Eilam of Tel-Aviv University, we are testing
the hypothesis that this quinpirole-induced transformation represents
an animal model of obsessive-compulsive disorder (OCD).
addition to research on psychostimulants and behavior, I am studying
brain mechanisms of schizophrenia using Positron Emission Tomography
(PET ). One current project focuses on identifying the neuronal
circuits which can produce auditory hallucinations in human subjects.
Dvorkin A, Silva C, McMurran T, Bisnaire L, Foster J, Szechtman H. Features of compulsive checking behavior mediated by nucleus accumbens and orbital frontal cortex. Eur J Neurosci. 2010 Nov;32(9):1552-63. doi: 10.1111/j.1460-9568.2010.07398.x. Epub 2010 Aug 22.
Woody EZ, Szechtman H.Adaptation to potential threat: the evolution, neurobiology, and psychopathology of the security motivation system. Neurosci Biobehav Rev. 2011 Mar;35(4):1019-33. Epub 2010 Aug 19. Review.
Hinds AL, Woody EZ, Drandic A, Schmidt LA, Van Ameringen M, Coroneos M, Szechtman H.The psychology of potential threat: properties of the security motivation system. Biol Psychol. 2010 Oct;85(2):331-7. Epub 2010 Aug 17.
Dvorkin A, Szechtman H, Golani I. Knots: attractive places with high path tortuosity in mouse open field exploration. PLoS Comput Biol. 2010 Jan 15;6(1):e1000638. PubMed PMID: 20090825; PubMed Central PMCID: PMC2796396.
- Zor R, Keren H, Hermesh H, Szechtman H, Mort J, Eilam D. Obsessive-compulsive disorder: a disorder of pessimal (non-functional) motor behavior. Acta Psychiatr Scand. 2009 Oct;120(4):288-98. Epub 2009 Mar 8. PubMed PMID: 19291081.
- Zor R, Hermesh H, Szechtman H, Eilam D. Turning order into chaos through repetition and addition of elementary acts in obsessive-compulsive disorder (OCD). World J Biol Psychiatry. 2009;10(4 Pt 2):480-7. PubMed PMID: 17853263.
- Beerepoot P, Lam V, Luu A, Tsoi B, Siebert D, Szechtman H. Effects of salvinorin A on locomotor sensitization to D2/D3 dopamine agonist quinpirole. Neurosci Lett. 2008 Dec 3;446(2-3):101-4. PubMed PMID: 18824069.
- Culver KE, Szechtman H, Levant B. Altered dopamine D2-like receptor binding in rats with behavioral sensitization to quinpirole: effects of pre-treatment with Ro 41-1049. Eur J Pharmacol. 2008 Sep 11;592(1-3):67-72. Epub 2008 Jul 4. PubMed PMID: 18644362; PubMed Central PMCID: PMC2577911.
- Dvorkin A, Culver KE, Waxman D, Szechtman H, Kolb B. Effects of hypophysectomy on compulsive checking and cortical dendrites in an animal model of obsessive-compulsive disorder. Behav Pharmacol. 2008 Jul;19(4):271-83. PubMed PMID: 18622174.
- Perreault ML, Graham D, Scattolon S, Wang Y, Szechtman H, Foster JA. Cotreatment with the kappa opioid agonist U69593 enhances locomotor sensitization to the D2/D3 dopamine agonist quinpirole and alters dopamine D2 receptor and prodynorphin mRNA expression in rats. Psychopharmacology (Berl). 2007 Nov;194(4):485-96. Epub 2007 Jul 10. PubMed PMID: 17619861.
- Perreault ML, Seeman P, Szechtman H. Kappa-opioid receptor stimulation quickens pathogenesis of compulsive checking in the quinpirole sensitization model of obsessive-compulsive disorder (OCD). Behav Neurosci. 2007 Oct;121(5):976-91. PubMed PMID: 17907829.
- Szechtman H, Woody EZ. Obsessive-compulsive disorder as a disturbance of security motivation: constraints on comorbidity. Neurotox Res. 2006 Oct;10(2):103-12. Review. PubMed PMID: 17062372.
- 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. Psychosis pathways converge via D2high dopamine receptors. Synapse. 2006 Sep 15;60(4):319-46. Review. PubMed PMID: 16786561.
- Perreault ML, Graham D, Bisnaire L, Simms J, Hayton S, Szechtman H. Kappa-opioid agonist U69593 potentiates locomotor sensitization to the D2/D3 agonist quinpirole: pre- and postsynaptic mechanisms. Neuropsychopharmacology. 2006 Sep;31(9):1967-81. Epub 2005 Oct 12. PubMed PMID: 16237381.
- Dvorkin A, Culver KE, Szechtman H. Differential effects of clorgyline on sensitization to quinpirole in rats tested in small and large environments. Psychopharmacology (Berl). 2006 Jul;186(4):534-43. Epub 2006 May 11. PubMed PMID: 16758240.