title: Corticotropin-releasing hormone (CRH) antisense oligodeoxynucleotide induces anxiolytic effects in rat.
abstract: Antisense oligodeoxynucleotide complementary to the start coding region of rat corticotropin releasing hormone (CRH) mRNA was intracerebroventricularly infused into rats three times at 12-h intervals. In the shuttle-box avoidance procedure antisense-treated rats showed, within 6 h, significant acceleration and increase in the total number of discriminative avoidance responses compared with controls, treated with the corresponding sense probe or vehicle alone. Following the shuttle-box experiment hypothalamic CRH hybridization signals and immunoreactivity were reduced, while CRH immunoreactivity in the median eminence remained unchanged. Plasma ACTH and corticosterone were decreased in antisense-treated animals. It is likely that in addition to a selective blockade of CRH translation, antisense treatment may also interrupt secretion of CRH. Antisense targeting of the hypothalamo-hypophysial-adrenal axis may provide new strategies for the neuropharmacology of affective disorders.
authors.affiliation: Max Planck Institute of Psychiatry, Clinical Institute, Munich, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Skutella
authors.forename: H
authors.initials: H
authors.lastname: Criswell
authors.forename: S
authors.initials: S
authors.lastname: Moy
authors.forename: J C
authors.initials: JC
authors.lastname: Probst
authors.forename: G R
authors.initials: GR
authors.lastname: Breese
authors.forename: G F
authors.initials: GF
authors.lastname: Jirikowski
authors.forename: F
authors.initials: F
authors.lastname: Holsboer
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001483:Base Sequence; D002552:Cerebral Ventricles; D003346:Corticotropin-Releasing Hormone / Q000235:genetics*; D007263:Infusions, Parenteral; D008297:Male; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D014151:Anti-Anxiety Agents; D016376:Oligonucleotides, Antisense; D003346:Corticotropin-Releasing Hormone