Effects of haloperidol and amisulpride on motor and cognitive skill learning in healthy volunteers

Abstract

The effects of a typical neuroleptic, haloperidol (1 and 2 mg orally), of an atypical neuroleptic, amisulpride (50 and 100 mg) and of a placebo on motor and cognitive skill learning were assessed in 60 healthy volunteers using repeated testing on the Tower of Toronto puzzle. Subjects were asked to solve three blocks of eight trials and, at distance from drug administration, a fourth block. The puzzle was connected to a computer in order to obtain a precise timing of individual moves. Two components of cognitive skill learning were assessed, the ability to learn to solve the puzzle and the acquisition of a problem-solving routine. Subjective feelings of effort and automatisation of the task were assessed using a questionnaire. Like placebo-treated subjects, neuroleptic-treated subjects were able to acquire a motor skill, to learn to solve the puzzle and to acquire a routine. However, haloperidol 2 mg-treated subjects needed significantly more moves to solve the puzzle in blocks 3 and 4, some of them having routinised a non-optimal solution. A significant cognitive slowing was observed in the haloperidol 1 mg group in block 4. The performance pattern and verbal reports suggested that haloperidol impaired the higher cognitive functions such as the ability to shift from one strategy to another and/or to assess one's performance accurately, possibly leading to the development of compensatory strategies. The only deleterious amisulpride effect was a cognitive slowing in block 4, which was observed in the lower dose group.

Noradrenaline blockade specifically enhances metacognitive performance

“…We took great care in the design of the study to render the two drug conditions as comparable as possible. First, because of the slightly different absorption rates, we administered amisulpride 30 min before propranolol, in keeping with previous drug schedules (Peretti et al, 1997; Ramaekers et al, 1999; Strange et al, 2003; Silver et al, 2004; Strange and Dolan, 2004; Hurlemann et al, 2005; Alexander et al, 2007; Gibbs et al, 2007; De Martino et al, 2008; Kahnt et al, 2015; Kahnt and Tobler, 2017). Second, to render the cognitive effects of the drugs as similar as possible, we selected dosages that were commonly reported in previous studies of neurocognition (i.e.…”

A review of the pharmacokinetics, tolerability and pharmacodynamics of amisulpride in healthy volunteers

“…Finally, no pharmacodynamic interactions impacting psychomotor performance were detected after the concurrent administration of 50 mg or 200 mg of amisulpride with 0.8 g/kg of ethanol or 2 mg of lorazepam to young subjects (Mattila et al, 1996;Perault et al, 1998). In contrast, haloperidol induced signi®cant impairments in various tasks after single or repeated administrations either to young subjects (deterioration of performance in CTT, DAT and CRT at 3 h and 6 h, and VIG at 4 h and 7 h, after 4 mg (single dose) or 4 mg/day for ®ve days) (Figures 3±5, Table 2) (Peretti et al, 1997;Ramaekers et al, 1999) or to elderly subjects (increase in detection time in VIG 9 h and 24 h after a single dose of 2 mg) ( Figure 2) (Legangneux et al, 2000). These marked deleterious effects are at variance with those observed after 400 mg amisulpride in young volunteers or after 50 mg and 200 mg in elderly subjects (Ramaekers et al, 1999;Legangneux et al, 2000).…”

“…Test 50 Single doses of 100 mg and 200 mg amisulpride were also free of deleterious effects on psychomotor performance and body sway (Mattila et al, 1996;Peretti et al, 1997;Perault et al, 1998). In another study (Legangneux et al, 2000), elderly subjects showed a signi®cant (p < 0.05) improvement in reaction time in a VIG test (digit vigilance task) after a 200 mg dose ( Figure 2).…”

“…Table 2. Central effects of a single oral dose of amisulpride or haloperidol as assessed in various psychomotor and performance tests in young volunteers (Ramaekers et al, 1999;Peretti et al, 1997) and in elderly volunteers (Legangneux et al, 2000) Amisulpride Haloperidol…”

“…Whichever dose of amisulpride is administered (50, 100, 200, or 400 mg), a single administration is without clinically relevant detrimental effects on working memory (Ramaekers et al, 1999;Legangneux et al, 2000), declarative memory (immediate free recall, delayed free recall, picture or word recognition) (Mattila et al, 1996;Perault et al 1998;Peretti et al, 1997;Legangneux et al, 2000), implicit memory (picture stem completion) (Peretti et al, 1997) and procedural memory (tower of Toronto) (Peretti et al, 1997). However, repeated administrations of amisulpride 400 mg/day to young subjects caused some working memory impairment 3 h and 6 h after dosing, and an increase in reaction time in the syntactic reasoning task, but this effect was nota-bly less than after single or multiple doses of 4 mg of haloperidol (Ramaekers et al, 1999).…”