QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.105.095810v1 317/3/1337    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jutkiewicz, E. M. Articles by Woods, J. H. Search for Related Content PubMed PubMed Citation Articles by Jutkiewicz, E. M. Articles by Woods, J. H.

BEHAVIORAL PHARMACOLOGY

The Convulsive and Electroencephalographic Changes Produced by Nonpeptidic -Opioid Agonists in Rats: Comparison with Pentylenetetrazol

Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan (E.M.J., M.G.B., J.H.W.); and Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland (J.E.F., K.C.R.)

-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 -opioid agonists at doses that previously were reported to produce antidepressant-like effects. In addition, -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 -opioid agonists [(+)-4-[(R)--[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-methoxyphenyl)methyl]-N,N-diethylbenz (SNC80) and [(+)-4-[(R)--[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-hydroxyphenyl)methyl]-N,N-diethylbenzamide [(+)-BW373U86]. Acute administration of nonpeptidic -opioid agonists produced bilateral ictal and paroxysmal spike and/or sharp wave discharges. -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 -opioid agonists. Overall, these data suggest that -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 -opioid agonist-induced convulsions. In terms of therapeutic development, these data suggest that it may be possible to develop -opioid agonists devoid of convulsive properties.

Address correspondence to: Dr. Emily M. Jutkiewicz, Department of Pharmacology, 1301 Medical Science Research Bldg. III, University of Michigan Medical School, Ann Arbor, MI 48109-0632. E-mail: ejutkiew{at}umich.edu

This article has been cited by other articles:

				E. M. Jutkiewicz The Antidepressant -like Effects of Delta-Opioid Receptor Agonists Mol. Interv., June 1, 2006; 6(3): 162 - 169. [Abstract] [Full Text] [PDF]