Changes in populations of cholinergic binding sites in brain after chronic exposure to barbital in rats

Abstract

Male rats were treated with barbital in their drinking fluid for about 40 weeks (daily dose 200 mg/kg). The treatment was stopped on day 0 and the number of muscarinic binding sites was measured in 3 brain parts (striatum; cortex and hippocampus; medulla oblongata and midbrain) during the abstinence with labeled quinuclidinyl benzilate (QNB) as ligand. Nicotine-like binding sites were quantified in the cortex with labeled tubocurarine. An increased number of QNB-binding sites was found in the striatum during the early part of the abstinence (days 0–3), followed by another increase later in the abstinence (days 12–21). In the cortex preparation a variable increase in QNB binding was measured from days 2–9 of the abstinence, whereas in the midbrain preparation the QNB binding was found to be increased only on day 9 in comparison to controls. A change in the proportion between high and low affinity muscarinic binding sites (measured by agonist-antagonist competition) was found in the cortex preparation during the period when the QNB binding was increased. Prior to the maximum abstinence convulsions the QNB binding was higher in rats without recorded spontaneous convulsions in comparison to rats with convulsions. A negative correlation between the time after the last convulsion and the number of QNB binding sites was observed in data from rats where the maximum convulsions had occurred before sacrifice. In addition, a negative relationship between the number of muscarine- and nicotine-like binding sites was found in the cortex during days 5–9 of the abstinence.