Expression profile and up-regulation of PRAX-1 mRNA by antidepressant treatment in the rat brain.
A protein associated with the peripheral-type benzodiazepine receptor (PRAX-1) has recently been cloned, but its regional distribution in the central nervous system and its function remain to be clarified. In situ hybridization was carried out to localize PRAX-1 mRNA in the rat brain and revealed a high expression of the transcript in limbic structures such as the CA1 region of the hippocampus, as well as the dentate gyrus, septum, amygdala, and the islands of Calleja. A dense hybridization signal was also observed in the nucleus accumbens, caudate nucleus, olfactory tubercle, pineal gland, and cerebellar cortex. PRAX-1 mRNA expression was largely neuronal; it colocalized with neuron-specific enolase but not glial fibrillary acidic protein. Long-term treatments (21 days) with the neuroleptic haloperidol increased PRAX-1 mRNA expression only in the dentate gyrus, whereas anxiolytic/anticonvulsant diazepam had no effect in any of the hippocampal region studied. Repeated electroconvulsive shock administration significantly enhanced PRAX1 expression in the CA1 subfield and dentate gyrus. Several classes of antidepressant treatment, including serotonin selective reuptake inhibitor (fluoxetine), mixed serotonin- and norepinephrine-uptake inhibitor (imipramine), and monoamine oxidase inhibitors (iproniazid and tranylcypromine), shared this effect. Furthermore, the selective nonpeptide NK2 receptor antagonist (S)-N-methyl-N-[4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl)butyl]benzamide (SR48968), which shows an antidepressant profile in animal studies, also enhanced PRAX-1 mRNA expression. These results point to a potential role of PRAX-1 function in the central nervous system and suggest that the up-regulation of PRAX-1 mRNA represents a common action of chronic antidepressant treatment.
Chardenot
Pascale
P
Central Nervous System Research Department, Sanofi-Synthélabo Recherche, Montpellier, France.
Roubert
Christine
C
Galiègue
Sylvaine
S
Casellas
Pierre
P
Le Fur
Gérard
G
Soubrié
Philippe
P
Oury-Donat
Florence
F
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011619:Psychotropic Drugs / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D000928:Antidepressive Agents; D002352:Carrier Proteins; D011619:Psychotropic Drugs; D012333:RNA, Messenger; C117357:TSPOAP1 protein, human