The effects of a benzodiazepine receptor antagonist beta-carboline ZK-93426 on scopolamine-induced impairment on attention, memory and psychomotor skills

Psychopharmacology (Berl). 1996 Feb;123(4):361-73. doi: 10.1007/BF02246647.

Abstract

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Arousal / drug effects
  • Attention / drug effects
  • Carbolines / pharmacokinetics
  • Carbolines / pharmacology*
  • Cognition / drug effects
  • Double-Blind Method
  • Electroencephalography / drug effects
  • GABA Antagonists / pharmacokinetics
  • GABA Antagonists / pharmacology*
  • GABA Modulators / pharmacology
  • GABA-A Receptor Antagonists*
  • Humans
  • Lorazepam / pharmacology
  • Memory / drug effects
  • Mental Processes / drug effects*
  • Parasympatholytics / antagonists & inhibitors*
  • Parasympatholytics / pharmacology*
  • Psychomotor Performance / drug effects
  • Scopolamine / antagonists & inhibitors*
  • Scopolamine / pharmacology*

Substances

  • Carbolines
  • GABA Antagonists
  • GABA Modulators
  • GABA-A Receptor Antagonists
  • Parasympatholytics
  • ZK 93426
  • Scopolamine
  • Lorazepam