[A TRH analog (DN-1417). Antagonistic effects on reserpine-induced decreases in local cerebral glucose utilization and cerebral monoamine levels].
Thyrotropin-releasing hormone (TRH) and its analog, DN-1417 (gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide citrate), significantly antagonized against reserpine-induced reduction of the spontaneous motor activity and the electroconvulsive threshold in mice. To search for sites of action and mechanisms, effects of DN-1417 on reserpine in local cerebral glucose utilization (LCGU) and cerebral monoamine levels were also investigated in rats. Reserpine (2 mg/kg, i.p., 24 hr pretreatment) reduced LCGU and the levels of cerebral monoamine in all the brain regions. DN-1417 (5 mg/kg, i.v.) significantly reversed the reduction of LCGU induced by reserpine in the thalamus dorsomedial nucleus, mamillary body, septal nucleus, caudate-putamen and nucleus accumbens. The effects of DN-1417 were completely abolished by pretreatment with a dopaminergic (DA) and a serotonergic (5-HT) receptor blocker, pimozide (1 mg/kg) and methysergide (5 mg/kg), respectively. DN-1417 (20 mg/kg, i.p.) reversed 5-HT level in the hypothalamus depleted by reserpine. These results suggest that the antagonistic effects of DN-1417 against reserpine-induced reduction of the locomotor activity and the electroconvulsive threshold seem to be mediated by DA- and 5-HT-ergic activations mainly in the nucleus accumbens and hypothalamus, respectively.
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002245:Carbon Dioxide / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010100:Oxygen / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000037:antagonists & inhibitors*; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology
D000927:Anticonvulsants; D002245:Carbon Dioxide; D013973:Thyrotropin-Releasing Hormone; D012110:Reserpine; C029762:DN 1417; D005947:Glucose; D010100:Oxygen