title: The selective delta opioid agonist SNC80 enhances amphetamine-mediated efflux of dopamine from rat striatum.
abstract: The highly selective delta opioid agonist, SNC80, elicits dopamine-related behaviors including locomotor stimulation and conditioned place-preference. In contrast, it has been reported that SNC80 fails to promote dopamine efflux from the striatum of freely moving rats. However, SNC80 does enhance behavioral responses to the stimulants, amphetamine and cocaine, suggesting an interaction between delta opioids and psychostimulants. Since the increase in locomotor activity elicited by amphetamine and related stimulants acting at the dopamine transporter is associated with increases in extracellular concentrations of dopamine within the striatum, we hypothesized that SNC80 enhances this activity by potentiating the overflow of dopamine through the transporter. To test this hypothesis, striatal preparations from Sprague Dawley rats were assayed for dopamine efflux in response to amphetamine challenge. SNC80 was given either in vivo or in vitro directly to rat striatal tissue, prior to in vitro amphetamine challenge. Both in vivo and in vitro administration of SNC80 enhanced amphetamine-mediated dopamine efflux in a concentration- and time-dependent manner. However, SNC80 in either treatment paradigm produced no stimulation of dopamine efflux in the absence of amphetamine. The effect of SNC80 on amphetamine-mediated dopamine overflow, but not the effect of amphetamine alone, was blocked by the delta selective antagonist, naltrindole and was also observed with other delta agonists. The results of this study demonstrate that even though SNC80 does not stimulate dopamine efflux alone, it is able to augment amphetamine-mediated dopamine efflux through a delta opioid receptor mediated action locally in the striatum.
authors.affiliation: Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Bosse
authors.forename: Emily M
authors.initials: EM
authors.lastname: Jutkiewicz
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Gnegy
authors.forename: John R
authors.initials: JR
authors.lastname: Traynor
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000493:pharmacokinetics; D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D001549:Benzamides / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000493:pharmacokinetics; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000502:physiology; D013347:Subcellular Fractions / Q000187:drug effects; D013997:Time Factors; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: D000701:Analgesics, Opioid; D001549:Benzamides; D018765:Dopamine Uptake Inhibitors; D009292:Narcotic Antagonists; D010879:Piperazines; D017465:Receptors, Opioid, delta; D014316:Tritium; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; D009271:Naltrexone; D020881:Enkephalin, D-Penicillamine (2,5)-; D000661:Amphetamine; C055382:naltrindole; D004298:Dopamine