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Pre-natal benzodiazepine exposure. III. Lorazepam exposure is associated with a shift toward inverse agonist efficacy

Division of Clinical Pharmacology, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Tufts University School of Medicine and New England Medical Center, Boston, MA 02111, USA

Lawrence G. Miller

Division of Clinical Pharmacology, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Tufts University School of Medicine and New England Medical Center, Boston, MA 02111, USA

Pre-natal exposure to benzodiazepines has been associated with neurobehavioral alterations in human and animal studies. To evaluate effects of pre-natal exposure on subsequent efficacy of benzodiazepine ligands, we exposed mice to lorazepam, 2 mg/kg/day, during days 14-20 of gestation and evaluated offspring at 6 weeks of age using pentylenetetrazol-induced convulsions. Mice exposed to lorazepam were similar to vehicle-exposed and untreated mice in pentylenetetrazol threshold. However, lorazepam-exposed mice had a reduced threshold after an acute dose of lorazepam compared to vehicle-exposed and untreated mice. For the proconvulsant inverse agonist compound FG 7142, threshold was also reduced after pre-natal lorazepam exposure compared to the other treatment groups. These data indicate that pre-natal lorazepam exposure is associated in mature mice with a shift in benzodiazepine efficacy toward the inverse agonist range of the benzodiazepine spectrum.

Key Words: lorazepam • benzodiazepine • pre-natal • inverse agonist

Journal of Psychopharmacology, Vol. 7, No. 1 suppl, 39-42 (1993)
DOI: 10.1177/026988119300700107


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