Dopamine receptor modulation of repetitive grooming actions in the rat: potential relevance for Tourette syndrome.
Studies of rodent grooming can provide valuable insight for dopamine contributions to the initiation, organization, and repetition of motor patterns. This information is useful for understanding how brain dysfunctions contribute to movement disorders such as Tourette syndrome and obsessive compulsive disorder, in which patients are driven to reiterate particular movement patterns. In rodents, dopamine D1 receptor stimulation causes a complex behavioral super-stereotypy in the form of excessive production and rigid execution of whole sequences of movements known as syntactic grooming chains. Sequential super-stereotypy of grooming chains may be particularly advantageous for modeling movement sequences and treatments in Tourette syndrome and related disorders. Here, we report that co-administration of haloperidol, one available treatment for Tourette syndrome and primarily a D2 receptor antagonist, prevented D1 stimulation with SKF38393 from inducing sequential super-stereotypy, which manifests as an exaggeration of the tendency to complete all four phases of a syntactic chain in rigid serial order once the first phase has begun. In a separate experiment, we showed that in contrast to acute D1 agonist administration, 39h withdrawal from chronic (3weeks) administration of the D1 antagonist SCH23390 (which has been suggested to increase D1 receptor expression in the basal ganglia) did not elicit sequential super-stereotypy after drug cessation. Instead, rats suddenly removed from repeated SCH23390 spent more time performing simple stereotypies that included intense scratching and biting behaviors. Together, these results have implications for understanding how dopamine receptors facilitate particular stereotypies manifest in animal models of Tourette syndrome and obsessive compulsive disorder.
Taylor
Jennifer L
JL
Department of Psychology, University of Michigan, Ann Arbor, MI48109-1043, USA. tayljenn@umich.edu
Rajbhandari
Abha K
AK
Berridge
Kent C
KC
Aldridge
J Wayne
JW
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001552:Benzazepines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D006120:Grooming / Q000187:drug effects* / Q000502:physiology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology; D005879:Tourette Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D006220:Haloperidol; D004298:Dopamine