Suppression of sex behavior by kappa opiates and stress steroids occurs via independent neuroendocrine pathways

• We challenge the hypothesis that κ-opiates suppress behavior via corticosterone pathway.
• Corticosterone and κ-opiates influence the same behavior via two independent pathways.
• A CB1 antagonist did not reverse κ-opioid behavioral effects.
• A κ-opioid antagonist did reverse κ-opioid behavioral effects.

Endocannabinoids and their receptors are found throughout the brain of all vertebrates. By virtue of their wide distribution, endocannabinoids have the potential to affect many behaviors. Prior research has shown that cannabinoids inhibit courtship-clasping and mediate behavioral responses to stress in male rough-skinned newts, Taricha granulosa, and cannabinoid signaling is initiated by rapid actions of the steroid corticosterone (CORT) at its specific membrane receptor (mCR). This same mCR also recognizes κ-opioid receptor agonists and antagonists. Prior behavioral studies show that κ-opioid agonists suppress clasping behavior in a dose dependent manner. Combined, these studies suggest that κ-opioid agonists might suppress clasping behavior via the same pathway initiated by CORT: up-regulation of endocannabinoid signaling. We examined whether pretreatment with a CB1 antagonist, AM281, would block κ-opioid-mediated suppression of clasping. We found that the CB1 antagonist did not reverse κ-opioid-induced suppression of clasping, revealing that while endocannabinoids mediate CORT-induced suppression of clasping, endocannabinoids do not mediate the κ-opioid-induced suppression of clasping.