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Scopolamine has been used as a pharmacologic model for cognitive impairments in dementia and Alzheimer's disease. The validity of this model seems to be limited because findings in animals do not readily translate to novel treatments in humans. Biperiden is also a cholinergic deficit model for cognitive impairments but specifically blocks muscarinic M1 receptors. The effects of scopolamine and biperiden (and pirenzepine) are compared in animal studies and related to findings in humans. It is concluded that the effects on cognitive functions are different for scopolamine and biperiden, and they should be considered as different cognitive deficit models. Scopolamine may model more advanced stages of Alzheimer's disease whereas biperiden may model the early deficits in declarative memory in aging and mild cognitive impairment.

Several types of stress can increase vulnerability to developing depression. This depression may be caused by the effects of stress on the serotonergic system, which may make the system more vulnerable. The aim of this experiment was to evaluate whether chronic mild stress (CMS) resulted in long-lasting vulnerability of the serotonergic system, reflected by stronger behavioural responses to a serotonergic challenge with acute tryptophan depletion (ATD) several weeks after the CMS had ended. Male Wistar rats were exposed to 3 weeks of CMS followed by a 2-week resting period. CMS resulted in blunted weight gain and lower sucrose consumption. After the resting period, rats were repeatedly treated with a gelatin-based protein-carbohydrate mixture, either with or without L-tryptophan, to acutely challenge the serotonergic system and the rats were tested in several tests of anxiety-elated and depression-related behaviour and memory. CMS and ATD both influenced behaviour on some tests, but overall this CMS procedure did not result in increased sensitivity to ATD, as there were no CMS x ATD interaction effects on behaviour. In conclusion, CMS did not result in long-lasting vulnerability of the serotonergic system, measured by the behavioural response to ATD several weeks after the CMS had ended. Behavioural Pharmacology 19:706-715

We examined the effects of DOI (2,5-dimethoxy-4-iodoamphetamine), 8-OH-DPAT (8-hydroxy-2-(N,N-dipropylamino)tetralin, eticlopride and amphetamine in a reaction time (RT) task. In this task a trial is initiated after a rat pushes a panel. Rats have to wait (0.5-1.5 s) until a tone is presented before making a response. The number of premature responses, releasing the panel before tone was switched on, was taken as a measure of motor impulsivity. A group of 10 Lewis rats was tested in the RT task after treatment with different doses of drugs which have been shown previously to affect impulsive responding: DOI (0.1, 0.2 mg/kg), 8-OH-DPAT (0.1, 0.3 mg/kg), eticlopride (0.01, 0.03 mg/kg) and D-amphetamine (0.3, 1 mg/kg). A progressive ratio test was used to control for drug effects on food motivation. DOI (0.1 mg/kg) and D-amphetamine (0.3 mg/kg) increased impulsive responding in the RT task. Conversely, 8-OH-DPAT decreased impulsive responding in the RT task. These effects of DOI, D-amphetamine and 8-OH-DPAT on impulsive responding were not associated with changes in food motivation, as assessed by performance in the progressive ratio task. Eticlopride did not affect impulsive responding. The present data suggest that 5-HT2A receptors and dopamine (but not D2 receptors) are associated with motor impulsivity.

The present study was designed to examine the effects of haloperidol (0.03, 0.1 mg/kg, intraperitoneal (i.p.)) and d-amphetamine (0.3, 1.0 mg/kg, i.p.) in a cone field task in which spatial working and reference memory (WM and RM, respectively) were assessed simultaneously. The apparatus is a large open field in which 16 cones are placed with four cones baited by placing a food reward in the top. After food-deprived rats had acquired this task they showed a high level of performance, that is avoided visits to non-baited cones (RM) and made few revisits to baited cones (WM). Haloperidol had a greater negative effect on RM than on WM performance, but also decreased the number of food rewards collected. On the other hand, the high dose of d-amphetamine induced a clear WM performance deficit, whereas RM performance was only marginally affected. The present study suggests that spatial discrimination performance can be dissociated using the measures RM and WM in the present task. Further, the deficits induced by haloperidol and d-amphetamine may not be specifically related with impaired mnemonic functions.