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L-prolyl-l-leucyl-glycinamide and its peptidomimetic analog 3(R)-[(2(S)-pyrrolidylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide (PAOPA) attenuate haloperidol-induced c-fos expression in the striatum.
- Source :
-
Peptides [Peptides] 2000 Feb; Vol. 21 (2), pp. 301-8. - Publication Year :
- 2000
-
Abstract
- Acute treatment of rats with haloperidol results in a rapid and transient increase in striatal c-fos mRNA and Fos immunoreactivity. The induction of immediate early genes by haloperidol may be involved in the development of extrapyramidal side effects. L-Prolyl-L-leucyl-glycinamide (PLG, or MIF-1) has been observed to antagonize the development of haloperidol-induced D(2) receptor supersensitivity in rats. We investigated the modulatory effects of PLG on haloperidol-induced c-fos and Fos protein expression in the rat striatum. We report that coadministration of either PLG or the potent analog of PLG, 3(R)-[(2(S)-pyrrolidylcarbonyl)amino]-2-oxo-1-pyrrolidineacetam ide (PAOPA), attenuated haloperidol-induced c-fos and Fos expression. Haloperidol induced [2 mg/kg, intraperitoneally (i.p.)] c-fos and Fos expression by 500% and 100%, respectively. These responses were attenuated by 170% and 75%, respectively, when coadministered with PLG (20 mg/kg, i.p.) or by 79% by PAOPA (10 microg/kg, i.p.).
- Subjects :
- Animals
Gene Expression Regulation drug effects
Haloperidol antagonists & inhibitors
Haloperidol pharmacology
MSH Release-Inhibiting Hormone analogs & derivatives
Male
Molecular Structure
Peptides pharmacology
Proto-Oncogene Proteins c-fos metabolism
RNA, Messenger drug effects
Rats
Rats, Sprague-Dawley
Corpus Striatum drug effects
Hormone Antagonists pharmacology
MSH Release-Inhibiting Hormone pharmacology
Proto-Oncogene Proteins c-fos genetics
Pyrrolidinones pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0196-9781
- Volume :
- 21
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Peptides
- Publication Type :
- Academic Journal
- Accession number :
- 10764960
- Full Text :
- https://doi.org/10.1016/s0196-9781(99)00194-1