Received for publication April 5, 2007.
Revised November 2, 2007.
Accepted for publication November 5, 2007.

The delta-opioid receptor agonist SNC80 synergistically enhances the locomotor-activating effects of some psychomotor stimulants, but not direct dopamine agonists in rats

Abstract

The nonpeptidic delta-opioid agonist SNC80 produces many stimulant-like behavioral effects in rodents and monkeys, such as locomotor stimulation, generalization to cocaine in discrimination procedures, and antiparkinsonian effects. Tolerance to the locomotor-stimulating effects of SNC80 develops after a single administration of SNC80 in rats; it is not known if cross-tolerance develops to the effects of other stimulant compounds. In the initial studies to determine if SNC80 produced cross tolerance to other stimulant compounds, it was discovered that amphetamine-stimulated locomotor activity was greatly enhanced in SNC80-pretreated rats. This study evaluated acute cross-tolerance between delta-opioid agonists and other locomotor-stimulating drugs. Locomotor activity was measured in male Sprague-Dawley rats implanted with radiotransmitters, and activity levels were recorded in the home cage environment. Three hour SNC80 pretreatment produced tolerance to further delta-opioid receptor stimulation, but also augmented greatly amphetamine-stimulated locomotor activity in a dose dependent manner. Pretreatments with other delta-opioid agonists ((+)BW373U86 and oxymorphindole) also modified amphetamine-induced activity levels. SNC80 pretreatment enhanced the stimulatory effects of the dopamine/norepinephrine transporter ligands cocaine and nomifensine, but not the direct dopamine receptor agonists SKF81297 and quinpirole. In conclusion, SNC80 enhanced the locomotor-stimulating effects of monoamine transporter ligands suggesting that delta-opioid receptor activation might alter the functional activity of monoamine transporters or presynaptic monoamine terminals.

Key words: SNC80, activity, amphetamine, delta-opioid, dopamine, rats