Stimulation of central histaminergic transmission attenuates diazepam-induced motor disturbance on rota-rod and beam walking tests in mice.
Behav Pharmacol
; 35(6): 351-365, 2024 Sep 01.
Article
in En
| MEDLINE
| ID: mdl-39051902
ABSTRACT
Diazepam administration has been shown to influence the release of histamine in various brain areas involved in motor behavior. Therefore, the present study explored the plausible regulatory role of the central histaminergic system in diazepam-induced deficits in motor performance in mice using the rota-rod and beam walking tests. In this study, several doses of diazepam (0.5, 1, 2, and 3â
mg/kg, i.p.) were assessed in mice for changes in motor performance on the rota-rod and beam walking test. In addition, the brain histamine levels were determined after diazepam administration, and the diazepam-induced motor deficits were assessed in mice, pretreated centrally (intracerebroventricular) with histaminergic agents such as histamine (0.1, 10â
µg), histamine precursor (L-histidine 0.1, 2.5â
µg), histamine neuronal releaser/H 3 receptor antagonist (thioperamide 0.5, 10â
µg), H 1 and H 2 receptor agonist [2-(3-trifluoromethylphenyl) histamine (FMPH 0.1, 6.5â
µg; amthamine 0.1, 5â
µg)/antagonist (H 1 cetirizine 0.1â
µg) and (H 2 ranitidine 50â
µg)]. Results indicate that mice treated with diazepam at doses 1, 2â
mg/kg, i.p. significantly increased the brain histamine levels. Moreover, in mice pretreated with histaminergic transmission-enhancing agents, the diazepam (2â
mg/kg, i.p.)-induced motor incoordination was significantly reversed. Contrastingly, diazepam (1â
mg/kg, i.p.) in its subeffective dose produced significant motor deficits in mice preintracerebroventricular injected with histamine H 1 and H 2 receptor antagonists on both the employed tests. Therefore, it is postulated that endogenous histamine operates via H 1 and H 2 receptor activation to alleviate the motor-impairing effects of diazepam.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Histamine
/
Diazepam
Limits:
Animals
Language:
En
Journal:
Behav Pharmacol
Journal subject:
CIENCIAS DO COMPORTAMENTO
/
FARMACOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
India
Country of publication:
United kingdom