EFFECTS OF RESTRAINT STRESS ON COMPONENTS OF ADENYLYL-CYCLASE SIGNAL-TRANSDUCTION IN THE RAT HIPPOCAMPUS

Chronic stress can injure hippocampal neurons as well as alter hippoca mpal function. The adenylyl cyclase (AC) signal transduction system is an important modulator of neurotransmission in this brain region. Thi s study was conducted to begin to understand the effects of chronic st ress on the hippocampal AC system. To assess dependence of type I and type II AC mRNA expression on adrenal integrity, total RNA was prepare d from the hippocampus of nonstressed rats 7 days following either sha m surgery or adrenalectomy (ADX). Adrenalectomy resulted in a 60% dimi nution in steady-state expression of type II AC mRNA (p < .005) and a nonsignificant fall in type I AC mRNA expression. Both sham and adrena lectomized rats were then exposed to 1-hour sessions of restraint, twi ce per day (0800 to 0900 and 1500 to 2600 hours) for 4 days. Following the stress paradigm, RNA was prepared from the hippocampus and type I and type II AC mRNA levels determined by Northern blot. Densitometic analysis showed that in comparison to unstressed sham rats, stressed s ham rats had a significant twofold increase in steady-state levels of type I and type II mRNA. Stressed adrenalectomized rats also had incre ased expression in type II AC mRNA but no significant stress-induced c hange in expression of type I AC mRNA. To assess dependence of hippoca mpal membrane G-Proteins on adrenal integrity, hippocampal membranes f rom nonstressed rats 7 days following either sham surgery or adrenalec tomy (ADX) were analyzed by immunoblot. Adrenalectomy resulted in a 25 % diminution in membrane Gsa content (p < .05), but ADX did not signif icantly change membrane Gi(1)alpha, Gi(2)alpha, G beta(36) or Go alpha content. In Sham animals, the stress paradigm resulted in increased l evels of membrane Gs alpha, Go alpha and G beta. Adrenalectomy blocked the effects of stress an these G-protein changes. Restraint stress di d not modulate the levels of Gi(1)alpha or Gi(2)alpha. Restraint stres s induced a small but significant increase in both AC activity and cAM P levels in hippocampus of both sham and adrenalectomized rats. In sum mary, components of the hippocampal AC signal transduction system and Goer are modulated by factors released during stress.