Effects of antisense to the (alpha)2A-adrenoceptors administered into the region of the locus ceruleus on behaviors in plus-maze and sexual behavior tests in sham-operated and castrated male rats.
Clinical and experimental findings have implicated brain alpha2-adrenoceptors in the regulation of many physiological functions, including sexual activity and stress-related behavior. However, which subtypes of the three alpha2-adrenoceptors that have now been cloned (alpha2A, alpha2B, and alpha2C) are involved in these controls have yet to be established. Here, we investigated the contribution of alpha2A-adrenoceptors of the locus ceruleus, the principal source of brain noradrenaline, to exploratory and sexual behaviors. Using administration of antisense oligodeoxynucleotide to inhibit the receptor expression, we found that reductions in brainstem alpha2A-adrenoceptor mRNA levels and alpha2-adrenoceptor densities induced by antisense treatment were not accompanied by any changes in the major characteristics of male sexual activity, such as mount latencies and numbers of mounts. However, in sexual behavior tests, antisense-treated male rats had decreased numbers of rearings and thus have higher percentages of behaviors positively correlated with sexual activity. Besides, antisense-treated animals had decreased anxiety in plus-maze tests. The data demonstrate that inhibition of alpha2A-adrenoceptor expression in the region of the locus ceruleus has an anxiolytic-like effect and facilitates male's attention to female in sexual behavior test.
Shishkina
G T
GT
Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk 630090, Russia.
Kalinina
T S
TS
Sournina
N Y
NY
Dygalo
N N
NN
D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000517:prevention & control; D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D001933:Brain Stem / Q000187:drug effects* / Q000378:metabolism; D003000:Clonidine / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008845:Microinjections; D009638:Norepinephrine / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage*; D009919:Orchiectomy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics; D012726:Sexual Behavior, Animal / Q000187:drug effects*
D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2; D003000:Clonidine; D004298:Dopamine; D009638:Norepinephrine