Possible neuronal mechanisms involved in neurotensin-induced catalepsy in mice.
The neuronal mechanisms of neurotensin (NT)-induced catalepsy were investigated in mice. NT administered intracerebroventricularly (ICV 0.5, 1.0 and 2.0 micrograms) produced catalepsy in a dose-dependent fashion. A significant effect was observed at 2.0 micrograms and a maximal effect 2-3 h after injection. The NT-induced catalepsy was inhibited by pretreatment with atropine, trihexyphenidyl or biperiden (each drug, 0.8-5.0 mg/kg, IP), anticholinergic drugs, and L-DOPA (100, 200 mg/kg, IP). However, the catalepsy was not significantly antagonized by p-chlorphenylalanine (300 mg/kg X 3 days, IP) or methysergide (5, 10 mg/kg, IP), antiserotonergic drugs, and was not potentiated by the GABAergic drugs, aminooxyacetic acid (25 mg/kg, IP) or muscimol (1 mg/kg, IP). In addition, the NT-induced catalepsy was dose-dependently reduced by antihistamines, such as diphenhydramine (0.8-10 mg/kg, IP) and tripelennamine (0.4-5.0 mg/kg, IP) and was potentiated after treatment with histidine (250, 500 mg/kg, IP), a precursor of brain histamine. NT-induced catalepsy was also reduced by ICV pretreatment with diphenhydramine (1-5 micrograms/rat), a H1 antagonist, but not by cimetidine (5, 20 micrograms/rat), a H2 antagonist. These findings suggest that the catalepsy induced by NT may involve not only central cholinergic and dopaminergic mechanisms but also a histaminergic mechanism mediated via H1-histamine receptors, and seems to differ from the catalepsy induced by neuroleptics.
D000818:Animals; D002375:Catalepsy / Q000139:chemically induced / Q000503:physiopathology*; D004347:Drug Interactions; D006220:Haloperidol / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000187:drug effects*; D009496:Neurotensin / Q000494:pharmacology*
D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D009496:Neurotensin; D006220:Haloperidol