The delta opioid agonist, SNC80, enhances amphetamine‐mediated release of dopamine through an action on glutamate neurotransmission

Abstract

The delta opioid agonist SNC80 augments amphetamine (AMPH)-mediated behaviors and AMPH-mediated dopamine release by a local action in the striatum, yet does not induce dopamine release alone. Glutamate is known to cause the release of dopamine and NMDA receptors have been shown to be located on dopamine nerve terminals in the striatum. Therefore, we tested the hypothesis that SNC80 acts indirectly via the glutamatergic system to enhance AMPH-mediated dopamine release. In rat striatal slices, glutamate caused dopamine release alone in a concentration-dependent manner and synergistically enhanced the amount of dopamine released in response to 100 μM AMPH. The glutamate-evoked dopamine release was enhanced in the absence of Mg2+, to relieve the ion conductance inhibition of NMDA receptors. Also in the absence of Mg2+, SNC80 (10 μM) both elicited dopamine release alone and produced a greater enhancement of AMPH-mediated dopamine release. The effect of SNC80 on AMPH-mediated dopamine release, but not the effect of AMPH alone, was attenuated in the presence of a 10 μM concentration of the selective NMDA antagonist (+) MK801. Thus SNC80 modulates dopamine release through a mechanism which involves glutamate activation of NMDA receptors. Supported by NIDA grants DA04087 (JRT) and F31 DA19728 (KEB).