Opiate-like actions by intracerebroventricular histamine in mice

Abstract

Analgesia, catalepsy, head twitch response and hypothermia were observed after intracerebroventricular (i.e.v.) histamine in mice. These symptoms are also seen when morphine and opioid peptides are injected into animals. Histamine has been known to have a role in the tolerance and physical dependence to morphine. In the current study, we examined the opiate-like effects by i.e.v. histamine, especially using catalepsy as an index. The results are as follows: i.e.v. histamine causes cataleptic state in a dose dependent manner (5-1000μg). H1-histamine receptor blocking agents such as pyrilamine, diphenhydramine and cyproheptadine reduced the cataleptic scores in a dose-dependent manner (5-20mg/kg, i.p.). However, H2-histamine receptor blocking agents such as Cimetidine and metiamide have no influence on it (10-100μg, i.e.v.). These results showed the action of histamine is mediated through H1-receptor in the case of catalepsy. Some antidepressants without iprindole reduced the catalepsy and showed their utility as H1-histamine receptor blocking agents. We also investigated certain mechanism of catalepsy in connection with other neurotransmitters. In the central cholinergic system, muscarinic steps are involved in its action since atropine and sparteine reduced the catalepsy, but mecamylamine is without effect. Naloxone reduced the catalepsy (5-10mg/kg). These results showed actions of histamine may stimulate the cholinergic and opioid systems.