The
delta opioid receptor agonist
SNC80 produces both antinociceptive and
antidepressant effects in rodents. This profile suggests that
SNC80 may also reverse prodepressant effects of
pain. Accordingly, this study compared
SNC80 effects in complementary assays of
pain-stimulated and
pain-depressed behavior in rats.
Intraperitoneal injection of dilute
acid served as an acute noxious visceral stimulus in rats to stimulate abdominal stretching (a
pain-stimulated behavior) or depress intracranial self-stimulation of the medial forebrain bundle (ICSS; a
pain-depressed behavior). When administered once per week to minimize acute tolerance,
SNC80 (1-10 mg/kg IP) decreased
acid-stimulated stretching but had little effect on
acid-induced depression of ICSS. More frequent
SNC80 administration produced tolerance to
SNC80 effects on
acid-stimulated stretching, but unmasked antinociception in the assay of
acid-depressed ICSS.
SNC80 did not facilitate ICSS in the absence of
pain, and effects of
SNC80 were not duplicated by ARM390, a reputed delta agonist congener of
SNC80 that does not internalize
delta receptors. These findings support continued consideration of delta agonists as candidate
analgesics to treat prodepressant effects of
pain and illustrate the potential for diametrically opposite effects of
drug treatments on preclinical measures of
pain-stimulated and
pain-depressed behavior.
PERSPECTIVE: The delta
opioid agonist
SNC80 blocked
pain-related depression of intracranial self-stimulation in rats, suggesting that delta agonists may be useful to treat prodepressant effects of
pain. Repeated
SNC80 produced tolerance to
SNC80 antinociception in a conventional assay of
pain-stimulated behavior but unmasked
SNC80 antinociception in an assay of
pain-depressed behavior.