Neurochemical manipulation of procedural memory: Sequential stimuli learning under influence of phentermine and pentobarbital

Within the scope of implicit, procedural memory research a large number of empirical studies have been conducted to explore the conditions under which structured sequence learning will emerge in healthy volunteers. Up to now, a few studies have been carried out to determine the effects of scopolamin e tan anticholinergic drug and lorazepam on procedural memory functions. Th e present study is concerned with the question whether procedural memory fu nctions will also be affected by centrally acting drugs that exert their ef fects on mechanisms involved in a general state of alertness or attention. For this purpose 24 subjects were treated, double-blind, with phentermine 2 0 mg (a derivative of amphetamine, known to increase the concentrations of dopamine and noradrenaline), pentobarbital 100 mg (a GABA agonist), or a pl acebo. Each subject performed a task wherein a structured sequence of items was presented during 24 repetitions. The task consisted of two levels of s equence complexity ('easy' and 'hard') and two levels of pacing (2 and 4 s) . MANOVA revealed interaction effects between the drugs and the repetitions of the sequences, indicating that learning of the sequences as a function of the repetitions was improved by phentermine and impaired by pentobarbita l. This effect was marginally significant for phentermine in comparison to both pentobarbital and placebo. Further, as a function of the repetitions, a significant decrement in sequence learning was found for pentobarbital on ly under slow pacing (4 s), in interaction with both levels of sequence com plexity, indicating that the learning and retention of procedural knowledge was more retarded in the 'hard' than in the 'easy' task condition. Moreove r, the results also provide a contribution to experimental procedures that appear to influence procedural memory functioning. It was found that additi onal effort caused by fast (2 s) pacing, hampers sequence learning in the ' hard' condition, highlighting that external pacing, sequence length and pat tern complexity caused differential effects on procedural memory functionin g. Copyright (C) 1999 John Wiley & Sons, Ltd.