Effects of antisense oligodeoxynucleotide to the alpha2A-adrenoceptors on the plasma corticosterone level and on elevated plus-maze behavior in rats.
Antisense strategy was used to investigate the role of alpha2A-adrenoceptor (alpha2A-AR) subtype in anxiety-related behavior. A 18-mer phosphorothioate oligodeoxynucleotide (AS-ODN) complementary to the alpha2A-AR mRNA was administered to the adult male rats for 3 days (1 nmol/5 microl/day) into the region of locus coeruleus (LC). Control groups received infusions of either oligodeoxynucleotide of a random sequence (RS-ODN) or saline. Treatment with AS-ODN significantly reduced the levels of alpha2A-AR mRNA in the brain stem. At the same time, AS-ODN treatment caused only a small reduction in [(3)H]clonidine binding (by 26-32%) in the brain stem which was not significant. Compared to both RS-ODN and saline controls, treatment with AS-ODN significantly increased the percentage of open arm entries in the elevated plus-maze while the total number of arm entries was unaltered. Also, AS-ODN treatment elevated basal levels of plasma corticosterone by 217% and 96% compared to both RS-ODN and saline controls. These changes in the hormone concentrations were at a level of marginal significance (p<0.1 versus random group). Taken together, the data indicate that administration of AS-ODN against alpha2A-ARs in the LC significantly reduced expression of alpha2A-AR mRNA in brain stem, moderately increased plasma corticosterone and had anxiolytic-like effect in the elevated plus-maze.
Shishkina
G T
GT
Institute of Cytology and Genetics, RAS, Novosibirsk 630090, Russia. gtshi@bionet.nsc.ru
Kalinina
T S
TS
Sournina
N Yu
NY
Saharov
D G
DG
Kobzev
V F
VF
Dygalo
N N
NN
D000316:Adrenergic alpha-Agonists / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D003000:Clonidine / Q000378:metabolism; D003345:Corticosterone / Q000097:blood*; D008125:Locus Coeruleus; D008297:Male; D008845:Microinjections; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000316:Adrenergic alpha-Agonists; D016376:Oligonucleotides, Antisense; D018341:Receptors, Adrenergic, alpha-2; D003000:Clonidine; D003345:Corticosterone