Expression Profile and Up-Regulation of Prax-1 mRNA by Antidepressant Treatment in the Rat Brain
- Pascale Chardenot,
- Christine Roubert,
- Sylvaine Galiègue,
- Pierre Casellas,
- Gérard Le Fur,
- Philippe Soubrié and
- Florence Oury-Donat
- Florence Oury-Donat, Sanofi-Synthélabo Recherche, C.N.S. Research Department, 371 rue du Professeur J. Blayac, F-34184 Montpellier Cédex 04, France. E-mail: florence.oury-donat{at}sanofi-synthelabo.com.
Abstract
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.
Footnotes
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P.R. and C.R. contributed equally to this work.
- Abbreviations:
- PRAX-1
- peripheral benzodiazepine receptor-associated protein 1
- CNS
- central nervous system
- 5HT
- serotonin
- NE
- noradrenaline
- CREB
- cAMP response element-binding protein
- BDNF
- brain-derived neurotrophic factor
- ECS
- electroconvulsive shock
- DG
- dentate gyrus
- SR48968
- (S)-N-methyl-N-[4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl) butyl]benzamide
- SR48965
- (R)-N-methyl-N-[4-acetylamino-4-phenypiperidino)-2-(3,4-dichlorophenyl)butyl]benzamide
- RT-PCR
- reverse transcription-polymerase chain reaction
- NSE
- neuron-specific enolase
- PBS
- phosphate-buffered saline
- dig
- digoxigenin
- SSC
- standard saline citrate buffer
- GFAP
- glial fibrillary acidic protein
- TNT
- Tris-HCl/NaCl/Tween 20
- TSA
- tyramide signal amplification
- HRP
- horseradish peroxidase
- PBR
- peripheral-type benzodiazepine receptor
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- Received June 24, 2002.
- Accepted September 10, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
