The endogenous neuropeptides cortistatin-14 (CST-14) and somatostatin-14 (SST-14) structurally resemble closely although they originate from different genes. Moreover, CST-14 is known to interact with the various somatostatin receptors. We recently showed in rats that intracere-broventricular (i.c.v.) administered SST-14 is anticonvulsant against pilocarpine-induced seizures, and that SST-14 elevated the hippocampal dopamine (DA) and serotonin (5-HT) levels as measured with in vivo microdialysis coupled to microbore liquid chromatography. Both the SST-14 mediated anticonvulsant effects and increases in hippocampal monoamines were abolished with the selective somatostatin sst2 receptor antagonist CYN154806, demonstrating the involvement of the sst2 receptor in the anticonvulsant effects and suggesting a role for DA and 5-HT as pharmacodynamic markers for the efficacy of anticonvulsant action. In the present experiments, we also show clear anticonvulsant effects of both i.c.v. (10 nmol/h) and various intrahippocampally (0.1, 1, 10, 30 mM) administered doses of CST-14 against pilocarpine-induced convulsions in rats. I.c.v. or intrahippocampal administration of CST-14 did not alter the extracellular hippocampal 5-HT levels and even tended to decrease the extracellular DA concentrations in the hippocampus. Thus, CST-14, similar to SST-14, possesses anticonvulsant effects in the pilocarpine rat model for limbic seizures. In contrast to the monoaminergic modulation observed for SST-14, elevations in hippocampal DA or 5-HT do not contribute to the CST-14-mediated anticonvulsant action. Further work is necessary to unravel the mechanisms of action and receptor subtypes involved in the anticonvulsant effects exerted by CST-14.