The effects of a benzodiazepine receptor antagonist beta-carboline ZK-93426 on scopolamine-induced impairment on attention, memory and psychomotor skills.
The effects of a single dose of scopolamine alone and in combination with ZK 93426 (a beta-carboline antagonist at the GABAA/BZ receptor complex with weak inverse agonist activity) were tested in two studies. In one study (study 1) the emphasis of enquiry was on different stages of information processing measured by a psychometric battery; in the second study (study 2) performance at different stages of memory and psychomotor abilities was tested and electroencephalogram recordings and video-tracking were also performed. Each study consisted of two parts, part I in which scopolamine (0.5 mg; 1 ml) or placebo were administered subcutaneously, and part II in which scopolamine (0.5 mg; 1 ml) was administered subcutaneously followed by an intravenous injection of ZK 93426 (0.04 mg; 0.04 ml/kg) or placebo. Thirty-six volunteers, who were randomly allocated to receive one of the two treatments (n = 18 per treatment), participated in each part. In study 1 attention was measured by a continuous attention task and a rapid information processing task, vigilance was measured by a visual vigilance task, and working memory and reasoning were evaluated by a logical reasoning task. A visual memory task was also included to measure acquisition and retention. In study 2 acquisition and short term storage and retrieval were measured by a word lists-Buschke restricted reminding procedure, and retention was tested by delayed recall and recognition. Psychomotor performance was assessed by measuring tapping speed (related to gross motoric abilities) and a pegboard task (related to fine motoric abilities). A task to measure working memory, the Pauli test, was also included. In study 1 scopolamine significantly impaired performance in the attentional and vigilance tasks (P < 0.05), but there was no effect in the logical reasoning task main measurements of time and accuracy. In study 2, scopolamine also impaired performance in the psychomotor tasks (P < 0.05) and the Pauli test. ZK 93426 partially antagonised most of the effects of scopolamine on memory and attention, suggesting that an interaction between the GABA-ergic and cholinergic systems is reflected in measurements of both attention and memory. In general a dissociation was found in the effects of scopolamine on memory, i.e. scopolamine impaired performance during all acquisition measurements but left retention unaffected.
Duka
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T
Experimental Psychology, University of Sussex, Brighton, UK.
Ott
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H
Rohloff
A
A
Voet
B
B
D000328:Adult; D001143:Arousal / Q000187:drug effects; D001288:Attention / Q000187:drug effects; D002243:Carbolines / Q000493:pharmacokinetics / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects; D018756:GABA Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006801:Humans; D008140:Lorazepam / Q000494:pharmacology; D008568:Memory / Q000187:drug effects; D008606:Mental Processes / Q000187:drug effects*; D010276:Parasympatholytics / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D012601:Scopolamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
D002243:Carbolines; D018756:GABA Antagonists; D018757:GABA Modulators; D058787:GABA-A Receptor Antagonists; D010276:Parasympatholytics; C042568:ZK 93426; D012601:Scopolamine; D008140:Lorazepam