No abstract

The effects of the muscarinic antagonists scopolamine HBr and MeBr, the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and the N-methyl-d-aspartate (NMDA) antagonists MK-801 and CGS-19755 on performance of rats in a delayed matching-to-position task were examined. Pretreatment with scopolamine HBr (0.05 and 0.1 mg/kg), resulted in a delay-dependent decrease in the percentage of correct responses and discriminability (log d), but had no effect on either the latency to complete trials, or the rate of trial completion during the fixed duration session. Scopolamine MeBr (0.1 mg/kg) did not impair percent correct or increase the response latency but did decrease the rate of trial completion. 8-OH-DPAT (up to 0.3 mg/kg), had no effect on percent correct, but did induce a small decrease in discriminability. The impairment in discriminability occurred only at a dose that substantially reduced the rate of trial completion. Both MK-801 (0.05 mg/kg) and CGS 19755 (10 mg/kg) induced a delay-independent impairment in percent correct, discriminability and a reduction in the rate of trial completion without affecting latency. A lower dose of CGS 19755 (5.0 mg/kg) induced a slight impairment in discriminability without significantly affecting the other measures. Taken together, these results demonstrate some dissociation between drug-induced cognitive and motor/motivational deficits in the DMTP test. However, the data question the specificity of putative cognitive impairments reported in many previous studies with the 5-HT1A agonist 8-OH-DPAT.

There is increasing interest in the potential functional role of the octapeptide angiotensin II (AII) in psychiatric and cognitive disorders. The novel angiotensin II (AII) receptor antagonists, losartan and PD123177, selective for the AT1 and AT2 receptor subtypes respectively, constitute important pharmacological tools for the assessment of the behavioural consequences of modulation of AII function. The present series of studies investigated the effects of each compound in two animal models of anxiety, the rat elevated zero-maze and mouse light/dark box, and two models of working memory in the rat, the operant delayed matching to position (DMTP) task and the spatial reinforced alternation test in the T-maze. Our data indicate that both compounds (0.01-10 mg/kg s.c.) were without significant effect in any of the behavioural assays. Using the present methods and strains of laboratory rodents, these findings provide no support for the involvement of AII receptor function in the mediation of anxiety of working memory.