Changes in neurotransmitter sensitivity in the mouse neocortical slice following propranolol and theophylline administration

1 The mouse neocortical slice has been used to examine the sensitivity of neurones to isoprenaline, 5‐hydroxytryptamine (5‐HT) and adenosine acutely and following chronic treatment of animals with propranolol or theophylline. 2 While having little effect alone, all three agonists enhanced the d.c. depolarizing potential produced by N‐methyl‐ d ‐aspartate (NMDA). The effect of (−)‐isoprenaline (0.2 μ m ) was shared by (+)‐isoprenaline at the much higher concentration of 10 μ m . 3 Superfusion of slices with theophylline or 8‐phenyltheophylline blocked responses to adenosine with evidence of selectivity. A single injection of theophylline 24 h before slice preparation did not alter agonist sensitivity, but when administered daily at 100 mg kg −1 for 14 days, the xanthine caused a loss of sensitivity to adenosine and (−)‐isoprenaline but not 5‐HT. The lower dose of theophylline, 10 mg kg −1 daily, also led to a loss of adenosine responses but no change of sensitivity to the amines. 4 Following the 14 day treatment with theophylline at 100 mg kg −1 daily in two groups of mice, responses to adenosine recovered to control levels after 20 days. 5 Propranolol superfusion blocked responses to both isomers of isoprenaline and 5‐HT but did not affect sensitivity to adenosine. 6 Chronic treatment with propranolol at 25 mg kg −1 daily for 14 days induced a loss of sensitivity to (−)‐isoprenaline and 5‐HT but not adenosine. A lower dose of 5 mg kg −1 daily caused no change in responses to adenosine or 5‐HT, but yielded an increased sensitivity to (−)‐isoprenaline. 7 The results are discussed with respect to reports of receptor up‐regulation in binding studies; caution is clearly required in extrapolating from such work to receptor activity in a functional system, especially in the case of theophylline and adenosine.