The temporal requirements for theophylline-induced upregulation of A1 adenosine receptors and elevation of seizure threshold were examined. Chronic theophylline exposure (75 mg/kg twice daily) elicited a significant upregulation of [3H]cyclohexyladenosine ([3H]CHA) binding sites following 7 and 14 days of treatment. Alterations in seizure threshold followed a similar temporal pattern of development. The reversibility of theophylline-induced upregulation of high affinity [3H]CHA binding sites was complete at 10 days following cessation of theophylline administration, while the alteration of seizure threshold required 21 days to return to control values.
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