Interaction of beta-adrenergic and somatostatinergic systems in the hippocampus has not been investigated fully. We studied the influence of DL-isoproterenol (ISO), a beta-adrenergic agonist and DL-propranolol (PRO), a beta-adrenergic blocking agent, on the somatostatinergic system in the rat hippocampus. The short-(5h) and long-term (14 days) administration of ISO (5 mg/kg i.p.) or of PRO (10 mg/kg i.p.) did not affect somatostatin-like immunoreactivity (SSLI) content in the hippocampus of male Wistar rats. Both short- and long-term ISO administration decreased the number of specific [125I]Tyr11-somatostatin ([125I]Tyr11-SS) receptors in synaptosomes from hippocampus (29%, P < 0.05 and 34%, P < 0.05, after short- and long-term administration, respectively) without changing the affinity constant. This decrease in the number of [125I]Tyr11-SS receptors was not due to a direct effect of ISO on these receptors since no decrease in binding was produced by high concentrations of ISO (10(-5) M) when added in vitro. In addition, this decrease could be blocked by pretreatment with PRO. Short- and long-term administration of PRO alone increased the [125I]Tyr11-SS binding in hippocampus (42%, P < 0.05 and 33%, P < 0.05, after short- or long-term administration, respectively) without changing the affinity constant. Although there is no direct evidence that the regulation of SS receptors by the beta-adrenergic system has a physiological significance, this mechanism may provide a means by which the brain environment could modulate SS receptor number and, therefore, sensitivity to SS in a subset of SS-sensitive neurons.