Search

It has been reported that selective GABA(B) receptor antagonists can enhance cognitive performance in a variety of learning paradigms. This prompted us to examine the effects of some more potent and newly synthesised GABAB antagonists CGP 71982, CGP 62349 and CGP 55845A in an active avoidance test in rats. A two-way active avoidance test with negative reinforcement was performed for the first 5 of 12 days of antagonist administration. CGP 71982 and CGP 55845A at all doses applied (0.01-1.0 mg/kg) had an improving effect on learning, and memory retention on day 12; the rats made more avoidances in both sessions compared to controls. CGP 62349 was only active at the lowest dose tested (0.01 mg/kg). The present study confirms that GABA(B) receptor antagonists can enhance cognitive performance but provides no insight into the mechanism of action of these novel antagonists.

The alpha(2)-adrenergic receptor agonist clonidine was examined for its ability to improve working memory in monkeys.Clonidine (0.116-34.8 microg/kg) was administered to six pigtail macaques in their performance of a computer-assisted delayed matching-to-sample (DMTS) task.During DMTS sessions initiated 1 hour after dosing, there was a slight improvement in mean task accuracy (long delay trials; 0.116-microg/kg). On the following day, there was continued and added improvement in accuracies associated with the long delay trials. On the day following 1.16-microg/kg, the entire memory retention curve was shifted to the right of vehicle. When the animals were again tested 48 hours after dosing (no pretreatment), these two patterns of task enhancement were continued and enhanced. Mean task accuracy associated with long delay trials was significantly increased by 14.2% trials correct when animals were originally treated with 0.116-microg/kg of clonidine. Mean task accuracy associated with medium delay trials was significantly increased by 11.8% trials correct when animals were treated with 1.16-microg/kg. On the sixth day after clonidine, task accuracies were still significantly improved during medium delay trials after 0.116-microg/kg. Median sample and choice latencies were not significantly influenced by clonidine treatment. These findings are consistent with the ability of clonidine to induce a protracted improvement in aspects of working memory.Early (attentional) and late (retention) components of memory appeared to be differentially sensitive to the dose of clonidine. Central alpha(2)-adrenergic receptors should be considered legitimate drug targets for future compound development for cognition enhancement.

Three experiments describe retroactive memory enhancement in chicks by chlorpromazine (CPZ), a potent membrane stabilizer at anesthetic doses. First, chicks trained on a one-trial peck suppression task under moderate aversant conditions and given 60--144 mg CPZ/kg, intraperitoneally, displayed increased memory retention 24 h later when compared with chicks given saline or 15--36 mg CPZ/kg. The second experiment confirmed the memory enhancement using a different moderate aversant on a different peck target and extended the effect to 48 h. The third experiment demonstrated the CPZ effect to be retrograde because the enhancement observed when CPZ was injected 1 min or 3 min after training did not occur when injection was delayed 4 h. One speculative interpretation of retrograde enhancement with CPZ includes the stabilization of swollen dendritic spines, which may facilitate neuronal pathways.

During the postnatal period, male Wistar rats were treated with orotate, either from the 6th to 15th, 16th to 25th, or 26th to 35th day of life. Learning and memory were tested in adulthood. Rats that received orotate from the 6th to 15th day showed a better retention of a learned brightness discrimination (Y-maze) than controls. An active avoidance (pole jumping) was learned more quickly by the rats orotate-treated from the 6th to 15th day than by controls. The spontaneous locomotor activity of previously orotate-treated rats was the same as in controls. Body weight measurements revealed no differences between orotate rats and control rats. The results suggest that memory retention in adulthood can be improved by postnatal orotate treatment.

The effect of methylglucamine orotate (MGO) on learning and memory was investigated in 24-month-old rats using brightness discrimination in a Y-chamber and active avoidance in a shuttle box. In both learning procedures, an improvement of memory retention following 5-day MGO treatment (225 mg/kg per day) was observed. The retention of untreated old animals was significantly lower compared to 8-week-old rats. MGO treatment resulted in a significant improvement of retention in old rats, which nearly compensated for their memory deficit.