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Title: Relating the behavioural teratological effects of benzodiazepines to their actions on membrane fluidity
Author: Kurishingal, H.
Awarding Body: University College of Swansea
Current Institution: Swansea University
Date of Award: 1994
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Studies on the impacts of prenatal exposure of Alderley Park strain mice to benzodiazepine receptor-influencing drugs on behavioural, biophysical and biochemical changes were examined in early neonatal life, with a view to throwing light on the molecular mechanisms underpinning the 'floppy infant syndrome'. Three benzodiazepine agonists (chlordiazepoxide, diazepam and bromazepam), the antagonist flumazenil (Ro 15-1788) or combinations of agonist (chlordiazepoxide or diazepam) with flumazenil or ethanol, were administered to mice in their third week of pregnancy. Pups exposed to 9-10 days of drugs gestationally were selected and cross-fostered to non-treated lactating dams. Pups exposed in these ways had slowed righting reflexes (hypotonia) and hypothermia. Both effects are classic symptoms of the 'floppy infant syndrome'. Both the agonists chlordiazepoxide and diazepam and the antagonist, flumazenil increased membrane fluidity in neural tissue. Flumazenil was, however, more effective in this respect than either of the agonists. When the agonists were administered in combination with either flumazenil or ethanol, their ability to fluidise the membrane was increased. Such changes in fluidity may result from biochemical changes in neural tissue. The most profound changes in neural cholesterol and phospholipid resulted after prenatal exposure to flumazenil, an action evident even when combinations of antagonist and agonist were administered. The biochemical and biophysical changes in neural tissue may account for the flacidity common in infants suffering from the 'floppy infant syndrome'. The model and the approach provide a fruitful way of examining the lasting behavioural impact of prenatal exposure to psychoactive drugs.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available