Rationale: 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.
Objective: 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)).
Methods: In an attempt to define the effects of opioid-receptor activation on the reward system, we used a social interaction test (after 21 days isolation). HPLC analysis was used to determine the monoamine and amino acid concentrations in reward-related structures.
Results: U-50488 (10.0 mg/kg), morphine (5.0 and 1.0 mg/kg), and naltrexone (5.0 mg/kg) decreased, and nor-BNI (10.0 mg/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.
Conclusions: 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.