High doses of @entity143 antagonists e.g. @entity3390 evoke @entity179 in rodents. To assess functional consequences of such treatment, three paradigms of two-way active avoidance learning (with visual or auditory conditioned stimuli) and additionally a spatial learning paradigm - radial maze - were used. Female @entity35 were treated i.p. with 5 mg/kg of @entity3390 . Recumbence, severe @entity2332 and @entity353 were observed for 3-7 days. Despite that, there were no statistically significant differences in performance of avoidance reaction between saline and @entity3390 treated animals trained 10-40 days after the drug administration. However, in the radial maze test (+) @entity3390 impaired reference (but not working) memory in the experiment that started 8 days after the treatment. Similar effect was observed on reversal learning. The clinically used @entity143 receptor antagonist @entity3393 at the doses of 20 and 40 mg/kg had also no such long term negative effect on working memory during training (even positive effect was seen at 20 mg/kg) but at 40 mg/kg impaired learning on the first day of reversal. This indicates that @entity3390 @entity2359 in the retrosplenial cortex is connected with subtle alterations in the learning performance that may be seen in some tests only. Moreover, @entity3393 doses greatly exceeding therapeutically relevant range produce minimal functional alteration. An additional experiment revealed that the same dose of @entity3393 results in two fold higher serum levels of the antagonist in female than male @entity35 . Hence, considering that profiling studies are done in male @entity35 , a safety factor of over 16 fold can be calculated for @entity3393 .

Behavioural evaluation of long-term @entity2359 effects of XXXX receptor antagonists.

@entity353 :: ('MESH:D015431', 'Disease') :: ['loss of body weight'] @entity3393 :: ('MESH:D008559', 'Chemical') :: ['memantine'] @entity2359 :: ('MESH:D020258', 'Disease') :: ['neurotoxicity'] @entity179 :: ('MESH:D019636', 'Disease') :: ['neurodegeneration in retrosplenial cortex'] @entity143 :: ('CHEBI:6121', 'Chemical') :: ['NMDA'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity3390 :: ('MESH:D016291', 'Chemical') :: ['MK-801', '(+)MK-801'] @entity2332 :: ('MESH:D007035', 'Disease') :: ['hypothermia']
@entity143 :: (CHEBI:6121,Chemical) :: ['NMDA']
