NEUROSTEROIDS AFFECT SPATIAL REFERENCE, WORKING, AND LONG-TERM-MEMORYOF FEMALE RATS

Female rats take longer to acquire a spatial task during behavioral es trus, when GABA-active progesterone and metabolites are elevated. Whet her neurosteroids and neuroactive steroids (neuro(active) steroids), w hich can act at GABA receptor complexes (GBRs), have activational effe cts on spatial/reference, working, and long-term memory was investigat ed. In Experiment 1, ovariectomized Long-Evans rats (N = 107) received oil vehicle or one of six neuro(active) steroids, with varying GBR ef ficacy (greatest to least efficacious: 5 alpha-pregnan-3 alpha-o1-20-o ne (THP), 5 alpha-pregnan-3 alpha-o1-11,20-dione, 4-pregnen-3,20-dione , 17 alpha-hydroxyprogesterone, 5-pregnen-3 beta-o1-20-one sulfate, an d 5-androstan-3 beta-o1-17-one sulfate (DHEAS). Following neuro(active ) steroid (3.2 or 6.4 mg/kg) or vehicle sc, rats were tested in a Morr is water maze, the following week in a Y maze, and then in an open fie ld. Neuro(active) steroid, but not vehicle, animals had decreased dist ances to the hidden water maze platform. THP (3.2 and 6.4 mg/kg) anima ls were faster to find this platform than vehicle animals. In the Y ma ze, 3.2 mg/kg THP increased percentage correct, but 6.4 mg/kg THP incr eased latencies to the goal box. DHEAS had the opposite effect, with 3 .2 mg/kg increasing latencies to the goal box, while 6.4 mg/ kg increa sed percentage correct. In Experiment 2, N = 75 ovariectomized rats we re icy implanted with one of the neuro(active) steroids or cholesterol vehicle and then tested for spatial/reference memory, working and lon gterm memory, and motoricity/anxiolysis as in Experiment 1. DHEAS impl ants decreased, while THP increased, latencies and distances to the hi dden platform in the Morris water maze. In the Y maze, THP increased l atencies and decreased percentage correct, but DHEAS increased the lik elihood of correct choice. Open field behavior of animals administered the various neuro(active) steroids (sc or icy) was not different. Thu s, of the neuro(active) steroids examined, the neurosteroids THP and D HEAS had the most pronounced activational affects on spatial/reference , working, and long-term memory, independent of motoricity. (C) 1995 A cademic Press, Inc.