Background: The decreased level of somatostatin and increased level of HISTAMINE are detected in the Parkinsonian brain. In old Wistar rats, the brain somatostatin deficiency can initiate catalepsy that suggests the pathogenic significance of this abnormality in Parkinson’s disease (PD). The ability of HISTAMINE to affect the somatostatin deficiency action is not studied.Objectives: The current study aimed to examine if HISTAMINE alters the cataleptogenic activity of the brain somatostatin deficiency in Wistar rats.Materials and Methods: The animals used in the study were 100 - 110 and 736-767 days old. Catalepsy was evaluated by the bar test. The inhibition of the brain somatostatin activity was simulated by I.C.V. administration of cyclosomatostatin (cycloSOM), a somatostatin receptor antagonist.Results: CycloSOM (0.2, 1.0, and 5.0 mg) and HISTAMINE (1.0 and 10.0 mg) alone were ineffective in both young and old animals. In combination, however, cycloSOM and HISTAMINE initiated cataleptic response in old rats. Effect of the combination was inhibited by H1 and H2 but not H3 antagonists.Conclusions: CycloSOM and HISTAMINE synergistically exert catalepsy in old rats. In light of these data, the combination of the decreased brain level of somatostatin and increased brain level of HISTAMINE may be of pathogenic relevance for extrapyramidal signs in PD.