NMDA receptor blockade attenuates locomotion elicited by intrastriatal dopamine D1-receptor stimulation.
Previous behavioral studies suggest that the striatum mediates a hyperactive response to systemic NMDA receptor antagonism in combination with systemic D1 receptor stimulation. However, many experiments conducted at the cellular level suggest that inhibition of NMDA receptors should block D1 receptor-mediated locomotor activity. Therefore, we investigated the consequences of NMDA receptor blockade on the ability of striatal D1 receptors to elicit locomotor activity using systemic and intrastriatal injections of the NMDA antagonist MK-801 combined with intrastriatal injections of the D1 full agonist SKF 82958. Following drug treatment locomotor activity was measured via computerized activity monitors designed to quantify multiple parameters of rodent open-field behavior. Both systemic (0.1 mg/kg) and intrastriatal (1.0 microg) MK-801 pretreatments completely blocked locomotor and stereotypic activity elicited by 10 microg of SKF 82958 directly infused into the striatum. Further, increased activity triggered by intrastriatal SKF 82958 was attenuated by a posttreatment with intrastriatal infusion of 1 microg MK-801. These data suggest that D1-stimulated locomotor behaviors controlled by the striatum require functional NMDA channels.
Kreipke
Christian W
CW
Cellular and Clinical Neurobiology Program, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Walker
Paul D
PD
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001552:Benzazepines / Q000008:administration & dosage; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000008:administration & dosage; D018491:Dopamine Agonists / Q000008:administration & dosage; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000187:drug effects
D001552:Benzazepines; D018491:Dopamine Agonists; D018691:Excitatory Amino Acid Antagonists; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; C071262:SK&F 82958