[The new tripeptoid neurotensin analog dilept selectively affects dopamine turnover in nucleus accumbens and hypothalamus].
The effects of dilept (N-caproyl-L-prolyl-L-tyrosine methyl ester) - a new peptidomimetic of neurotensine - on the level of monoamines and their main metabolites in four functionally important brain structures has been studied upon single and subchronic administration in intact rats and in those pretreated with the NMDA receptor blocker ketamine. Repeated administration of dilept favors the accumulation of DOPAC and accelerates the dopamine (DA) turnover in nucleus accumbens, as manifested by an increase in the DOPAC/DA ratio. The opposite effect (decrease in the DOPAC/DA ratio) was observed in the hypothalamus, where the subchronic treatment with dilept completely inhibited the activating action of ketamine on the DA turnover. The selective influence of dilept on the dopaminergic system activity in nucleus accumbens (but not in striatum), together with the previously obtained behavioral data, suggest that dilept is a new atypical neuroleptic producing no extrapyramidal side effects.
Retiunskaia
M V
MV
Kudrin
V S
VS
Klodt
P M
PM
Us
K S
KS
Gudasheva
T A
TA
Ostrovskaia
R U
RU
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001923:Brain Chemistry / Q000187:drug effects*; D004298:Dopamine / Q000032:analysis* / Q000378:metabolism; D007031:Hypothalamus / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D009496:Neurotensin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D009714:Nucleus Accumbens / Q000737:chemistry* / Q000378:metabolism; D009928:Organ Specificity / Q000187:drug effects; D011392:Proline / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
D014150:Antipsychotic Agents; C401484:GZR 123; D009496:Neurotensin; D014443:Tyrosine; D011392:Proline; D004298:Dopamine