The effect of aniracetam (Ro 13-5057, 1-anisoyl-2-pyrrolidinone) was studied on various forms of experimentally impaired cognitive functions (learning and memory) in rodents and produced the following effects: (1) almost complete prevention of the incapacity to learn a discrete escape response in rats exposed to sublethal hypercapnia immediately before the acquisition session; (2) partial (rats) or complete (mice) prevention of the scopolamine-induced short-term amnesia for a passive avoidance task; (3) complete protection against amnesia for a passive avoidance task in rats submitted to electroconvulsive shock immediately after avoidance acquisition; (4) prevention of the long-term retention- or retrieval-deficit for a passive avoidance task induced in rats and mice by chloramphenicol or cycloheximide administered immediately after acquisition; (5) reversal, when administered as late as 1 h before the retention test, of the deficit in retention or retrieval of a passive avoidance task induced by cycloheximide injected 2 days previously; (6) prevention of the deficit in the retrieval of an active avoidance task induced in mice by subconvulsant electroshock or hypercapnia applied immediately before retrieval testing (24 h after acquisition). These improvements or normalizations of impaired cognitive functions were seen at oral aniracetam doses of 10-100 mg/kg. Generally, the dose-response curves were bell-shaped. The mechanisms underlying the activity of aniracetam and its 'therapeutic window' are unknown. Piracetam, another pyrrolidinone derivative was used for comparison. It was active only in six of nine tests and had about one-tenth the potency of aniracetam. The results indicate that aniracetam improves cognitive functions which are impaired by different procedure and in different phases of the learning and memory process.

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It has been proposed that the nucleotide sequences of the 3' terminal extracistronic regions of phage RNA plus and minus strands have been strictly conserved during evolution because they are stringently required for recognition by the viral replicase. We The 5'-and 3'-terminal regions of Q13 RNA comprise nontranslatable sequences of 61 and >61 nucleotides, respectively (1-3). A similar situation obtains in the case of the RNA of the group I phages MS2, f2 and R17 (4-7). Although about 3% of the nucleotide positions in the coat cistron differ from one group I RNA to another (7-9), the terminal extracistronic regions, comprising more than 150 nucleotides, are invariant. This observation led to the proposal that the replication of these phages depends strictly on the primary structure of the extracistronic sequences (9); in particular it was suggested that the specific interaction of phage RNA with its cognate replicase is mediated by these regions (6) Mmol of Tris-HCl (pH 7.5), 4 Mmol of KCl, and 20 nmol of EDTA were added, giving a final volume of 20 A. After 15 min at 370, 10 IA were transferred to 10 M1 of a mixture of the same composition but containing no RNA template. After 15 min at 370, this procedure was repeated, for a total of nine transfers. Ten microliters of the 10th incubation and 2 units of replicase were added to 20 Al of fresh reaction mixture and incubation was continued for 30 min. Ten microliters of fresh mixture and 4 units of replicase were added, and after an additional 30 min another 30 pl of mixture were added and incubation was continued for a further 90 min. After extraction with an equal volume of phenol at 20°the aqueous layer was filtered through a column (7-mm diameter) of Sephadex G-50 (7 cm) and Chelex-100 Na+ (0.5 cm). The pooled excluded fractions were adjusted to 0.05 M Tris * HCl (pH 7.5), 0.1 M NaCl, 5 mM EDTA, and the RNA was precipitated with 2 volumes of ethanol at -10°and recovered by centrifugation (10,000 rpm in a Sorvall HB-4 rotor, 10 min at -10°).The RNA was dissolved in 150 MAl of 0.5 mM EDTA and centrifuged through .a 5-23% sucrose gradient in 50 mMTris-HCl (pH 7.5)-5 mM EDTA. The fractions containing 30S RNA were pooled and precipitated with ethanol and the RNA was dissolved in 20 Ml of water. The yield of RNA was 4 Mg. Two micrograms of this product were denatured and used as template to initiate a series of nine further transfers, as described above. A 2-Ml sample of each of the incubations (except for the 1st, 5th, 10th, and 21st) was taken to determine acid-insoluble radioactivity.Serial replication of wild-type Q# RNA (extracted from phage) was carried out in a similar fashion, except that incuba-