Delta opioid receptor (DOR) selective agonists hold promise clinically as analgesics, but their effects on seizures remain controversial. In this study we examined the effects of the DOR agonist, (+)-4-[(alpha R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethyl-benzamide (SNC80), on behavioral seizures and hippocampal histopathology in the pilocarpine model of temporal lobe epilepsy. Systemic administration of SNC80 (30 or 60 mg/kg) alone elicited brief seizures within minutes of injection in about half of all rats. When SNC80 (30 or 60 mg/kg) was given prior to pilocarpine administration, trends toward increased latencies to first seizure and status epilepticus (SE) were seen, which correlated with the incidence of a prior, brief SNC80-induced seizure. Significant dose-dependent effects of SNC80 also were observed. Prior administration of SNC80 (30 mg/kg) significantly decreased the number of rats exhibiting acute pilocarpine-induced seizures and overall seizure severity compared to rats given pilocarpine alone, suggesting that SNC80 was anticonvulsant. SNC80 (60 mg/kg) also decreased overall seizure severity. However, SNC80 (60 mg/kg) doubled the total seizure time and the number of rats exhibiting prolonged SE compared to pilocarpine alone, further suggesting that SNC80 has pro-convulsant properties. Significant effects of SNC80 on pilocarpine-induced seizures did not correlate with the occurrence of a prior SNC80-induced seizure. The degree of hilar neuron loss and mossy fiber sprouting correlated strongly with prolonged SE rather than dose of SNC80 (> or =60 min), suggesting that SNC80 did not dramatically alter pilocarpine-induced seizures in the absence of behavioral modifications. Our results demonstrate that the DOR agonist, SNC80, has complex, dose-dependent effects on pilocarpine-induced seizures.