Baseline Plasma GABA: Its Relationship to the Adverse Effects of Acute Lorazepam Administration on Cognition in the Elderly

Abstract:

The GABA system is an active target for drugs to treat a variety of disorders and the availability of an indirect measure of central GABA activity would not only enhance psychiatric research, but also permit assessment of the pharmacodynamic effects of drugs designed to act on this system. The relationships between plasma baseline pre-drug GABA concentrations and cognitive impairments induced by an acute oral dose of lorazepam (0.5 and 1.0 mg) were investigated in 22 healthy elderly individuals. Partial correlations controlling for plasma lorazepam concentrations revealed no significant relationship between baseline plasma GABA levels and lorazepam-induced impairments on tests of cognitive functioning. Plasma GABA concentration does not appear to be a useful marker of susceptibility to benzodiazepine-induced cognitive toxicity in the elderly. Other approaches to estimating central GABA activity should be pursued.

Document Type: Research article

DOI: 10.1007/s11064-004-7041-3

Affiliations: 1: Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd. Bldg. 35, Orangeburg, NY 10962, USA; Department of Psychiatry, New York University School of Medicine, New York, NY USA (), Email: Pomara@nki.rfmh.org 2: Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd. Bldg. 35, Orangeburg, NY 10962, USA 3: Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd. Bldg. 35, Orangeburg, NY 10962, USA; Department of Psychiatry, New York University School of Medicine, New York, NYUSA 4: Department of Psychiatry, Duke University Medical Center, UK 5: Cognitive Drug Research, Goring-on-Thames, Oxon, UK 6: Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd. Bldg. 35, Orangeburg, NY 10962, USA; Department of Psychiatry, New York University School of Medicine, New York, NY USA; Analytical Psychopharmacology Laboratories, New York State Psychiatric Institute; Department of Psychiatry, College of Physicians & Surgeons, Columbia University 7: Department of Pharmacology & Experimental Therapeutics, Tufts University School of Medicine, Boston, NY USA