A synergistic interaction between dopamine D1 and D2 receptor subtypes in the memory impairments induced by concussive brain injury (CBI) in mice.
Profound latent learning and memory deficits with increased monoamine levels in the brain following concussive brain injury (CBI) have been documented in our previous work. The purpose of the present study was to determine the role of dopamine (DA) receptor subtypes in the memory deficits associated with CBI. Profound latent learning and memory impairments were observed in the vehicle-treated CBI mice. SCH-23390 administered 15 min post-injury had no significant effects on the impairments of latent learning and memory in the CBI mice. Sulpiride significantly improved the impairments of latent learning and memory in a dose-dependent manner, indicating that activation of dopaminergic neuronal function is involved in the CBI-induced amnesia. Interestingly, co-administration of sulpiride and SCH-23390, at doses which alone has no significant effect, significantly ameliorated the impairments of latent learning and memory. These results strongly suggested that D1 and D2 receptor subtypes are synergistically involved in the dysfunction of learning and memory associated with CBI.
Tang
Y P
YP
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Japan.
Noda
Y
Y
Nabeshima
T
T
D000818:Animals; D001552:Benzazepines / Q000627:therapeutic use; D001924:Brain Concussion / Q000150:complications / Q000523:psychology*; D018492:Dopamine Antagonists / Q000627:therapeutic use*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D007859:Learning Disabilities / Q000188:drug therapy / Q000209:etiology; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D013469:Sulpiride / Q000627:therapeutic use
D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D013469:Sulpiride