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The selective delta opioid agonist SNC80 increases amphetamine‐mediated release of dopamine
Author(s) -
Bosse Kelly E,
Jutkiewicz Emily M,
Gnegy Margaret E,
Traynor John R
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a676-c
Subject(s) - naltrindole , dopamine , amphetamine , chemistry , striatum , pharmacology , agonist , endocrinology , medicine , opioid receptor , biochemistry , receptor
The delta opioid agonist SNC80 produces dopamine‐related behaviors including locomotor stimulation, antidepressant and anti‐Parkisonian like effects. In contrast, it has been reported that SNC80 fails to release dopamine from the striatum of freely moving rats (Longoni et al., 1998 Behav. Pharmacol., 9: 9). To address this apparent inconsistency, we first showed that SNC80 enhanced locomotor stimulation produced by the psychomotor stimulant amphetamine (AMPH). Second, since the locomotor activity elicited by AMPH is associated with an increase in extracellular concentrations of dopamine within the striatum, we hypothesized that SNC80 enhances AMPH‐induced locomotor activity by potentiating AMPH‐stimulated release of dopamine. To test this hypothesis, rats were given varying doses (3.2–32 mg/kg, i.p.) of SNC80 and 3 h later were sacrificed, striatal slices were prepared and assayed for the release of dopamine in response to AMPH challenge. SNC80 enhanced AMPH‐mediated dopamine release in a dose‐dependent manner. The effect of SNC80 on AMPH‐mediated dopamine release, but not the effect of AMPH alone, was blocked by a delta selective dose of the antagonist naltrindole. Similarly, addition of SNC80 (1–100μM) to striatal preparations of naïve rats, 30 min before AMPH challenge, resulted in an enhancement of dopamine release. The results of this study demonstrate that even though SNC80 is reported not to release dopamine alone, it is able to augment AMPH‐mediated dopamine release by a local action in the striatum. Supported by NIDA grants DA04087 (JRT) and 07267.