Vasopressin and corticotropin-releasing hormone gene responses to novel stress in rats adapted to repeated restraint

Stress-responsive neurons of the hypothalamic paraventricular nucleus (PVN) show functional plasticity and adapt to repeated restraint (RR) stress. To investigate whether neuronal adaptation to the homotypic stress also affec ts their response to a heterotypic stressor, we used in situ hybridization with intronic and exonic probes to measure primary transcript (hnRNA) and m essenger RNA (mRNA) levels for CRH and vasopressin (VP) in the PVN of contr ol and RR rats after the heterotypic stress of ip hypertonic saline injecti on (ipHS). Two weeks of daily restraint blunted plasma corticosterone and p arvocellular CRH, but not VP, transcript responses to a further restraint e pisode. IpHS increased circulating corticosterone in both groups, but level s were higher in RR rats. CRH hnRNA increased within 15 min and returned to baseline by 1 h in both naive and RR rats. CRH mRNA increased more slowly in both groups, peaking at 2 h, with RR rats showing greater responses at t his time. Parvocellular VP hnRNA reached a peak 2 h after ipHS in naive rat s, but more rapidly (1 h) and to higher levels in RR rats. The number of pa rvocellular neurons expressing VP hnRNA increased approximately 5-fold afte r ipHS in both groups. Basal VP mRNA levels and the number of parvocellular cells expressing VP mRNA were elevated in RR rats. Both ipHS and naive rat s showed an increase in VP mRNA transcripts after ipHS, with RR rats showin g greater levels at 2 and 4 h. Magnocellular cells in both PVN and supraopt ic nuclei showed increases in VP hnRNA within 15 min. The data demonstrate VP responses in parvocellular neurons of both control and RR rats, whereas profound inhibition of CRH transcription is selective for the homotypic str essor with CRH responsiveness to the heterotypic stress preserved or increa sed.