Temporal relationship between A1 adenosine receptor upregulation and alterations in bicuculline seizure susceptibility in rats

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.