Kappa Opioid Modulation of Serotonergic Neurotransmission in the Hypothalamus, Hippocampus and Striatum in the Male Rat

Objectives: We have investigated the modulatory effects of κ-opioid receptors on the central serotonergic system in the hypothalamus, hippocampus and striatum. Materials and Methods: Male Sprague-Dawley rats (n=32) used in the experiments were divided into four groups. Anaesthetized animals were mounted on a stereotaxic apparatus and intracerebroventricularly infused with U-50488H (κ-agonist, 50μg/kg), Nor-BIN (κ-antagonist, 50μg/kg) or U-50488H + Nor-BIN. Control group received saline alone. All animals were decapitated 30 mins after infusions. Hypothalamus, hippocampus and striatum were microdissected and snap frozen. Concentrations of 5-hydroxytryptamin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA, 5-HT metabolite) in these brain regions were determined by HPLC-ECD. Results: 5-HT and 5-HIAA values in the hypothalamus and hippocampus of U-50488H-treated group were significantly decreased compared to control group (p<0.01 and p<0.05). Indoleamine levels (ng/gr tissue) in the κ-antagonist group were found to be similar to or slightly lower than the control values (p<0.05). Nor-BIN reversed the U-50488H inhibition of 5-HT release in the agonist+antagonist treated group (p<0.001). 5-HT levels in the striatum of all three groups were significantly higher than control group (p<0.01), 5-HIAA concentrations in the same brain region significantly decreased (p<0.001). Ratio of 5-HIAA/5-HT in the hypothalamus, hippocampus and striatum was significantly (p<0.05 and p<0.001, respectively) lowered by the κ-agonist. Conclusion: These results suggest that κ-opioid receptors modulate serotonergic neurotransmission in the hypothalamus, hippocampus and striatum. ©2006, Fırat Üniversitesi, Tıp Fakültesi