title: Histamine- and haloperidol-induced catalepsy in aged mice: differential responsiveness to L-DOPA.
abstract: In rodents and dog, histamine induces catalepsy, a dopamine-dependent phenomenon that resembles the extrapyramidal signs of Parkinson's disease (PD). Histamine was also found to damage the dopaminergic neurons in rat substantia nigra. These facts, as well as an increase in brain histamine levels in Parkinsonian patients, suggest a pathogenic role for histamine in PD. As it seems, a comparison between pattern of experimental brain histamine toxicity and signs of PD would elucidate the role of histamine in PD pathogenesis.
  
  
  
  This study aimed to examine whether mouse histamine-induced catalepsy shares such age-related traits of PD as disease aggravation and underresponsiveness to 3,4-dihydroxy-L: -phenylalanine (L: -DOPA) in aged patients. For comparison purposes, haloperidol-induced catalepsy was studied.
  
  
  
  The intensity of catalepsy was measured as the time the mouse maintained an abnormal posture. The cataleptogens, histamine or haloperidol, were administered intracerebroventricularly and subcutaneously, respectively.
  
  
  
  The cataleptogenic activity of histamine was significantly higher in 18-19-month-old and 22-23-month-old mice than 3-4-month-old ones. Aging was found to decrease the responsiveness of the histamine-induced catalepsy to L: -DOPA. The intensity of the haloperidol-induced catalepsy and its sensitivity to L: -DOPA were found independent of the animal's age.
  
  
  
  The mouse histamine-induced catalepsy, unlike haloperidol-induced one, displays the same pattern of age dependency as PD. These findings support an involvement of histamine in the PD pathogenesis.
authors.affiliation: Centre on Theoretical Problems in Physical and Chemical Pharmacology, Russian Academy of Sciences, Leninsky Prospect 123-4-63, Moscow 117513, Russia. newrology@yandex.ru
authors.forename: Ilya D
authors.initials: ID
authors.lastname: Ionov
authors.forename: Nicholas N
authors.initials: NN
authors.lastname: Severtsev
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002375:Catalepsy / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D006632:Histamine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007980:Levodopa / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D013997:Time Factors
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa; D006632:Histamine; D006220:Haloperidol; D004298:Dopamine