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 selec-, 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.PRAX-1 has recently been isolated by the yeast two-hybrid system, using the peripheral-type benzodiazepine receptor (PBR) as bait (Galiegue et al., 1999). This 1857-amino acid protein is a single 220-to 250-kDa entity and is encoded by a 7.5-kilobase mRNA that is highly expressed in the central nervous system and at lower levels in some peripheral tissues. PRAX-1 was shown to interact with PBR in several cell lines, but this interaction has not yet been demonstrated in the central nervous system (CNS). Subcellular localization studies of PBR have shown that it is linked to mitochondria in the rat brain (Basile and Skolnick, 1986), as well as in the rat adrenal gland (Anholt et al., 1986) and many peripheral organs (Antkiewicz-Michaluk et al., 1988). More recently, the use of confocal microscopy further confirmed the abundant mitochondrial localization of PBR (Garnier et al., 1993). PRAX-1 protein was shown to be present in both mitochondrial and cytoplasmic compartments (Galiegue et al., 1999). A comparison of PRAX-1 and PBR expression profiles revealed that some tissues, like lung or testis, express PBR but are devoid of detectable PRAX-1 expression (Burgi et al., 1999). Furthermore, immunohistochemical analysis proved this protein to be highly expressed in the hippocampus, which demonstrates a very low level of PBR expression (Anholt et al., 1985). The...