Single intense prenatal stress reduce behavioural suppression in an operant conflict paradigm in the adult progeny. Influence of Metyrapone administration

Stressors presented during late prenatal period can have long-term effects on offspring behaviour (1). Indeed we showed that in the rat progeny a single immobilization procedure at gestational day 16 enhances spatial learning in a non-aversive, rewarded-facilitated learning task, the Can Test, and decreases anxiety-like behaviour in the elevated plus maze (2). In this study, we wanted to investigate: (i) the effects of a single prenatal immobilization-stress on the operant conflict task (OCT), an anxiety-related procedure, in which positively reinforced responses are suppressed by contingent punishment (3); (ii) the expression of mineralcorticoid and glucocorticoid receptors (MRs, GRs) in the hippocampus and hypothalamus under basal and shock-induced conditions; (iii) the influence of an acute manipulation of corticosterone levels with metyrapone on the OCT. Our results show that: prenatal stress enhances the number of the punished responses in the OCT (p<0.05); MRs are increased in the hippocampus of control rats (p<0, 05), while GRs are increased in the hypothalamus of prenatally stressed rats (p<0, 05), following electric shock-exposure; metyrapone administration (50mg/kg) diminished the number of the punished responses both in prenatally-stressed and in control rats (p<0, 05). These data confirm that a single prenatal stress induces in the progeny a greater ability to cope with conflict situations, probably due to the different distribution of glucocorticoid receptors in the rat brain. Metyrapone induces a higher sensitivity to the electric shock, in both rat groups, likely as a consequence of a reduction in corticosterone levels (4).1) Yang J. et al, Neurobiol Learn &amp; Mem 87 (2007) 257-2632) Cannizzaro C. et al, Behav Br Res 169 (2006) 128-136 3) Loiseau F. et al, Behav Pharmacol 14 (2003) 447-4554) Malgorzata L. et al, Behav Br Res 171 (2006) 189-198