title: Acute cocaine treatment increases thimet oligopeptidase in the striatum of rat brain.
abstract: Many studies indicate that thimet oligopeptidase (EC3.4.24.15; TOP) can be implicated in the metabolism of bioactive peptides, including dynorphin 1-8, α-neoendorphin, β-neoendorphin and GnRH. Furthermore, the higher levels of this peptidase are found in neuroendocrine tissue and testis. In the present study, we have evaluated the effect of acute cocaine administration in male rats on TOP specific activity and mRNA levels in prosencephalic brain areas related with the reward circuitry; ventral striatum, hippocampus, and frontal cortex. No significant differences on TOP specific activity were detected in the hippocampus and frontal cortex of cocaine treated animals compared to control vehicle group. However, a significant increase in activity was observed in the ventral striatum of cocaine treated-rats. The increase occurred in both, TOP specific activity and TOP relative mRNA amount determined by real time RT-PCR. As TOP can be implicated in the processing of many neuropeptides, and previous studies have shown that cocaine also alters the gene expression of proenkephalin and prodynorphin in the striatum, the present findings suggest that TOP changes in the brain could play important role in the balance of neuropeptide level correlated with cocaine effects.
authors.affiliation: Departamento de Biofísica, Universidade Federal de São Paulo, SP, Brazil.
authors.forename: Fernanda M
authors.initials: FM
authors.lastname: Dalio
authors.forename: Bruna
authors.initials: B
authors.lastname: Visniauskas
authors.forename: Eliane S
authors.initials: ES
authors.lastname: Bicocchi
authors.forename: Juliana C
authors.initials: JC
authors.lastname: Perry
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Freua
authors.forename: Tarsis F
authors.initials: TF
authors.lastname: Gesteira
authors.forename: Helena B
authors.initials: HB
authors.lastname: Nader
authors.forename: Maurício F M
authors.initials: MF
authors.lastname: Machado
authors.forename: Sergio
authors.initials: S
authors.lastname: Tufik
authors.forename: Emer S
authors.initials: ES
authors.lastname: Ferro
authors.forename: Monica L
authors.initials: ML
authors.lastname: Andersen
authors.forename: Cláudio A B
authors.initials: CA
authors.lastname: Toledo
authors.forename: Jair R
authors.initials: JR
authors.lastname: Chagas
authors.forename: Vitor
authors.initials: V
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D003342:Corpus Striatum / Q000201:enzymology*; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; C029992:proenkephalin; C033660:preproenkephalin; D008666:Metalloendopeptidases; C022510:thimet oligopeptidase; D003042:Cocaine