%0 Journal Article %A Emily M. Jutkiewicz %A Michelle G. Baladi %A John E. Folk %A Kenner C. Rice %A James H. Woods %T The Convulsive and Electroencephalographic Changes Produced by Nonpeptidic δ-Opioid Agonists in Rats: Comparison with Pentylenetetrazol %D 2006 %R 10.1124/jpet.105.095810 %J Journal of Pharmacology and Experimental Therapeutics %P 1337-1348 %V 317 %N 3 %X δ-Opioid agonists produce convulsions and antidepressant-like effects in rats. It has been suggested that the antidepressant-like effects are produced through a convulsant mechanism of action either through overt convulsions or nonconvulsive seizures. This study evaluated the convulsive and seizurogenic effects of nonpeptidic δ-opioid agonists at doses that previously were reported to produce antidepressant-like effects. In addition, δ-opioid agonist-induced electroencephalographic (EEG) and behavioral changes were compared with those produced by the chemical convulsant pentylenetetrazol (PTZ). For these studies, EEG changes were recorded using a telemetry system before and after injections of the δ-opioid agonists [(+)-4-[(αR)-α-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-methoxyphenyl)methyl]-N,N-diethylbenz (SNC80) and [(+)-4-[α(R)-α-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-hydroxyphenyl)methyl]-N,N-diethylbenzamide [(+)-BW373U86]. Acute administration of nonpeptidic δ-opioid agonists produced bilateral ictal and paroxysmal spike and/or sharp wave discharges. δ-Opioid agonists produced brief changes in EEG recordings, and tolerance rapidly developed to these effects; however, PTZ produced longer-lasting EEG changes that were exacerbated after repeated administration. Studies with antiepileptic drugs demonstrated that compounds used to treat absence epilepsy blocked the convulsive effects of nonpeptidic δ-opioid agonists. Overall, these data suggest that δ-opioid agonist-induced EEG changes are not required for the antidepressant-like effects of these compounds and that neural circuitry involved in absence epilepsy may be related to δ-opioid agonist-induced convulsions. In terms of therapeutic development, these data suggest that it may be possible to develop δ-opioid agonists devoid of convulsive properties. The American Society for Pharmacology and Experimental Therapeutics %U https://jpet.aspetjournals.org/content/jpet/317/3/1337.full.pdf