Dopamine-antagonistic, anticholinergic, and GABAergic effects on declarative and procedural memory functions

Declarative and procedural memory functions are related to dissociable neur oanatomic substrates. In the present study differential effects of pharmaco logically induced changes in dopaminergic, GABAergic, and cholinergic activ ity in the brain on declarative (object and face recognition, immediate and delayed word recall) and procedural memory processes (compensatory trackin g) were investigated. In a double-blind design, either 3 mg of haloperidol, 11 mg of midazolam, 1 mg of scopolamine, or placebo were administered to 8 0 healthy volunteers randomly assigned to one of the four drug conditions. Although all three drugs produced a detrimental effect on immediate and del ayed word recall, recall performance was substantially more impaired by the benzodiazepine midazolam than by either haloperidol or scopolamine. While recognition of faces was affected by neither of the drugs, performance on o bject recognition was significantly decreased by midazolam as compared to p lacebo. Procedural learning was markedly impaired by all drugs but, again, the observed effect was most pronounced with midazolam. Additional analyses of measures of subjective activation, cortical arousal, and psychomotor pe rformance argued against the assumption that the observed memory-impairing effects were secondary to drug-induced sedation. The overall pattern of res ults revealed that memory processes are much more susceptible to changes in GABAergic than in dopaminergic or cholinergic neurotransmitter activity. F urthermore, the present findings point to the conclusion that the modulatin g effects of dopaminergic, GABAergic, and cholinergic neurotransmitter syst ems on declarative and procedural memory functions are less specific than s uggested by neuropsychological studies in patients. (C) 2000 Elsevier Scien ce B.V. All rights reserved.