Changes in noradrenaline release and in beta receptor number in rat hippocampus following long-term treatment with theophylline or L-phenylisopropyladenosine

Abstract

The administration of a stable adenosine analogue, L-N6-phenylisopropyladenosine (L-PIA, 0.3 mg/kg i.p.), caused a decrease in the accumulation of L-DOPA in the rat hippocampus after blockade of aromatic amino acid decarboxylase by NSD 1015 [3-hydroxybenzylhydrazine] (150 mg/kg). The adenosine receptor antagonist theophylline (15 mg/kg) increased the L-DOPA accumulation. In slices from rat hippocampus L-PIA causes an inhibition of the stimulation-evoked release of [3H]-noradrenaline [norepinephrine] (NA). The magnitude of this effect was enhanced after 1 wk treatment with theophylline (15 mg/kg per day). The number of .beta.-adrenoceptors in the rat hippocampus, measured by binding of [3H]-dihydroalprenolol was significantly reduced after theophylline treatment, and tended to be higher after L-PIA treatment. Activation of adenosine receptors in vivo causes a decreased synthesis of NA in the rat hippocampus. The reason may be a reduced firing-rate of the NA-neurons. Theophylline enhanced the synthesis, possibly indicating a role for endogenous adenosine in the regulation of NA-turnover. Long-term treatment with these drugs caused adaptive changes in the presynaptic adenosine receptor activity and in the number of .beta.-adrenoceptors.