TY - JOUR T1 - Differential Behavioral Tolerance to the δ-Opioid Agonist SNC80 ([(+)-4-[(α<em>R</em>)-α-[(2<em>S</em>,5<em>R</em>)-2,5-Dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-methoxyphenyl)methyl]-<em>N</em>,<em>N</em>-diethylbenzamide) in Sprague-Dawley Rats JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 414 LP - 422 DO - 10.1124/jpet.105.088831 VL - 315 IS - 1 AU - Emily M. Jutkiewicz AU - Sarah T. Kaminsky AU - Kenner C. Rice AU - John R. Traynor AU - James H. Woods Y1 - 2005/10/01 UR - http://jpet.aspetjournals.org/content/315/1/414.abstract N2 - Nonpeptidic δ-opioid agonists produce a number of behaviors, such as antidepressant-like effects, locomotor stimulation, antinociception, and convulsions. To consider this class of compounds as potential therapeutics for humans, the effects of δ-opioid agonists after repeated administration must be evaluated. Therefore, the present study investigated the effects of repeated δ-opioid agonist, SNC80 ([(+)-4-[(αR)-α-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-methoxyphenyl)-methyl]-N,N-diethylbenzamide), administration on its antidepressant-like effects in the forced swim test, locomotor activity, and convulsions in male Sprague-Dawley rats. Tolerance developed rapidly to the convulsive and locomotor-stimulating effects of SNC80 but not to the antidepressant-like effects. In addition, tolerance was evaluated at the level of the receptor-G protein interaction by measuring 5′-O-(3-[35S]thio)triphosphate binding in brains from rats that were pretreated with SNC80. With various exposure durations to SNC80, some brain regions demonstrated tolerance at different times, suggesting that adaptations in the δ-opioid system may occur during agonist exposure. Overall, the lack of observable tolerance to the antidepressant-like effects of SNC80 indicates that this class of compounds has potential as a novel antidepressant therapy. The American Society for Pharmacology and Experimental Therapeutics ER -