Focused motor stereotypies do not require enhanced activation of neurons in striosomes.
Stereotypic motor behavior is a widespread phenomenon of many neurologic and psychiatric disorders. Studies on the mechanisms controlling motor stereotypies have focused on the role of dopamine in modulating the activity of basal ganglia neuronal circuits, and recent results demonstrated that stereotypic motor responses characteristic of psychomotor stimulant sensitization correlate with an enhanced activation of neurons located in striatal striosomes that substantially exceeds that of the surrounding matrix. The present study tested whether predominant striosomal activation is a general predictor for stereotypy. Wild-type and dopamine D(2) and D(3) receptor knockout mice were treated either three times with methamphetamine (METH; 3 x 5 mg/kg every 2 hours) or once with a full D(1) agonist. Depending on the genotype, both treatments elicit the same focused stereotypy (taffy pulling). Repeated METH-treatment elicits intense stereotypy in wild-type and D(3) mutants but not in D(2) single and D(2)/D(3) double mutants. The stereotypic response of wild-type and D(3) mutants correlates with a predominant activation of neurons located in striosomes. No striosomal predominance is detected in METH-treated D(2) single and D(2)/D(3) double mutants. In contrast, D(2) single and D(2)/D(3) double mutants exhibited the most severe stereotypic response to D(1)-agonist treatment. However, this treatment did not result in enhanced striosomal activation. Thus, whereas the expression of stereotypy in response to repeated METH treatment requires D(2) receptor expression, D(2) receptor expression diminishes stereotypic responses to an acute dose of a D(1) agonist. Enhanced striosomal activation, however, is a reliable indicator of D(1)- and D(2)-receptor coactivation but not a predictor for repetitive motor behavior in general.
Glickstein
Sara B
SB
Department of Psychiatry and Department of Neuroscience, Columbia University College of Physicians & Surgeons and New York State Psychiatric Institute, New York, New York 10032, USA.
Schmauss
Claudia
C
D000818:Animals; D001480:Basal Ganglia Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D019581:Neuropil / Q000187:drug effects / Q000378:metabolism; D011237:Predictive Value of Tests; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000172:deficiency / Q000235:genetics; D050637:Receptors, Dopamine D3; D019956:Stereotypic Movement Disorder / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics
D018491:Dopamine Agonists; C493594:Drd3 protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D008694:Methamphetamine; D004298:Dopamine