κ-opioid receptor as a key mediator in the regulation of appetitive 50-kHz ultrasonic vocalizations.

Abstract

Acute administration of high doses of morphine reduced 50-kHz ultrasonic vocalizations (USVs). Although morphine meets the classical criteria for inducing 50-kHz USVs (it causes place preference and induces dopamine release in nucleus accumbens), it also inhibits appetitive vocalizations. The aims of this study were to (i) study the pharmacological impact of κ-opioid (KOR) and μ-opioid receptor (MOR) ligands on the emission of 50-kHz USVs triggered by social interaction after long-term isolation and (ii) analyze the concentrations of the main neurotransmitters in reward-related structures (ventral tegmental area (VTA), nucleus accumbens (NAcc), and medial prefrontal cortex (mPFC)). In an attempt to define the effects of opioid-receptor activation on the reward system, we used a social interaction test (after 21days isolation). HPLC analysis was used to determine the monoamine and amino acid concentrations in reward-related structures. U-50488 (10.0mg/kg), morphine (5.0 and 1.0mg/kg), and naltrexone (5.0mg/kg) decreased, and nor-BNI (10.0mg/kg) increased 50-kHz USVs. Acute pretreatment with nor-BNI or naltrexone reduced the 50-kHz suppression induced via morphine. The biochemical data showed several variations between groups regarding dopamine concentrations, serotonin, and their metabolites; these data may suggest that the levels of emitted ultrasound in the 50-kHz band are inversely proportional to the 5-hydroxyindoleacetic acid (5-HIAA)/3-methoxytyramine (3-MT) ratio in the VTA. These results indicate an important role for KOR in the regulation of 50-kHz USV emissions and suggest that KOR activation may be a key mediator in the regulation of reward responses. Changes in the balance between serotonin and dopamine concentrations in the VTA may be a key predictor for 50-kHz USV emission.