Effects of MDL 73005 on water-maze performances and locomotor activity in scopolamine-treated rats

The stimulation of 5-HT1A receptors in the raphe or their blockade in the h ippocampus can reduce cognitive deficits induced by blockade of muscarinic receptors in the hippocampus. We investigated the effects of MDL 73005 (8-[ 2-(2,3-dihydro-1,4-benzodioxin-2-yl-methylamino) ethyl]-8-azaspiro[4,5] dec ane-7,9-dione methyl sulphonate), an agonist at 5HT(1A) somatodendritic aut oreceptors and an antagonist at postsynaptic 5-HT1A receptors in rats treat ed systemically with scopolamine. Spatial memory was assessed in a water ma ze using protocols testing reference and working memory. Home cage locomoto r activity was also determined. Working memory and locomotor activity were evaluated before and after para-chlorophenylalanine (pCPA) treatment. Scopo lamine produced a weak impairment of reference memory at 0.5 mg/kg, and a m ore pronounced impairment of working memory at 0.25 and 0.5 mg/kg. MDL 7300 5 alone (2 mg/kg, ip) had no effect, but prevented the memory impairments i nduced by 0.25 mg/kg of scopolamine. Scopolamine induced hyperlocomotion. M DL 73005 alone did not affect locomotor activity, but exacerbated the hyper locomotion induced by 0.5 mg/kg of scopolamine. pCPA did not abolish the ef fects of MDL 73005, suggesting that these effects were not due to an action at presynaptic receptors, or even that they involved receptors other than serotonergic ones (e.g., D-2). In conclusion, MDL 73005 is able to antagoni se moderate spatial memory dysfunctions induced by systemic muscarinic bloc kade. (C) 2001 Elsevier Science Inc. All rights reserved.