Alpha-helical CRF blocks differential influence of corticotropin releasing factor (CRF) on appetitive and aversive memory retrieval in rats

This study examined whether corticotropin releasing factor (CRF), given prior to test, would produce an improved retrieval of aversive memory in the same way as pre-exposure to inescapable footshocks and the CRF antagonist, alpha-helical CRF 9-41 (a-h CRF), blocks this effect in rats. For this purpose animals conditioned in a T-maze with appetitive (10% sucrose) and aversive (2.0 mA footshock) events were given intracerebroventricularly (i.c.v.) 20 min before testing, a single dose of 0.05, 0.1, 0.2 or 0.4 μg/rat of CRF, or 5 μg/rat of a-h CRF, or both at 10 min interval. In the retention test conducted with the same training apparatus 72-hr after conditioning, CRF (0.05, 0.1 and 0.2 μg) treated rats showed a dose-dependent increase in latencies to enter the previously shocked goalarm, with the absence of such a difference in responding to the nonshocked goalarm. The highest dose of CRF (0.4 μg), however, increased the latencies to enter both the goalboxes. Alpha-helical CRF, administered 10 min before, antagonized the memory-enhancing effect of CRF. Further, CRF (0.1, 0.2 and 0.4 μg) significantly decreased the total number of center entries in the open field, consistent with the view that i.c.v. administered CRF produces 'anxiogenic-like' effect. Alpha-helical CRF reversed this effect. The effect of CRF on memory retrieval was similar to that seen following inescapable footshock in rats. The results thus suggest the possible involvement of central CRF mechanisms in the differential enhancement of memory of helplessness condition.