Background and objective: Cognitive impairments have been reported in patients with hyperprolactinemia; however, there is a lack of knowledge of brain structure alterations relevant to hyperprolactinemia in prolactinomas. Thus, we aimed to identify changes in brain structure in prolactinomas and to determine whether these changes are related to cognitive performance and clinical characteristics. Methods: Participants were 32 female patients with prolactinomas and 26 healthy controls (HC) matched for age, sex, education, and handedness. All participants underwent magnetic resonance imaging brain scans, neuropsychological assessments, and clinical evaluations. Voxel-based morphometry analysis was used to identify changes in gray matter volume (GMV). Partial correlation analysis and multiple linear regression were performed to determine the relationship between GMV, cognition, and clinical characteristics. Results: Compared to HC, patients with prolactinomas demonstrated a decrease in GMV in the left hippocampus, left orbitofrontal cortex, right middle frontal cortex (MFC), and right inferior frontal cortex (IFC). In addition, patients performed worse than controls on tests for verbal memory and executive function, and this was significantly related to the GMV of the left hippocampus and right MFC, respectively. Moreover, in the patients, we found a negative relationship between serum prolactin levels and the GMV of the left hippocampus and right IFC, whereas a positive relationship was found between the GMV of the left hippocampus and serum levels of estradiol and luteinizing hormone. Conclusion: In patients with prolactinomas, specific brain structure abnormalities have been identified and are associated with cognitive impairments and dysfunctional hormones. This study enhances our understanding of brain structure changes that may occur with prolactinomas and provides novel and fundamental evidence for previous behavioral findings relevant to hyperprolactinemia.

The function of TRPV1 (transient receptor potential vanilloid subfamily, member 1) in the central nervous system is gradually elucidated. It has been recently proved to be expressed in nucleus accumbens (NAc), a region playing an essential role in mediating opioid craving and taking behaviors. Based on the general role of TRPV1 antagonist in blocking neural over-excitability by both pre- and post-synaptic mechanisms, TRPV1 antagonist capsazepine (CPZ) was tested for its ability to prohibit persistent opioid craving in rats. In the present study, we assessed the expression of TRPV1 in nucleus accumbens and investigated the effect of CPZ in bilateral nucleus accumbens on persistent morphine conditioned place preference (mCPP) in rats. We also evaluated the side-effect of CPZ on activity by comparing cross-beam times between groups. We found that morphine conditioned place preference increased the TRPV1 expression and CPZ attenuated morphine conditioned place preference in a dose-dependent and target–specific manner after both short- and long-term spontaneous withdrawal, reflected by the reduction of the increased time in morphine-paired side. CPZ (10 nM) could induce prolonged and stable inhibition of morphine conditioned place preference expression. More importantly, CPZ did not cause dysfunction of activity in the subjects tested, which indicates the inhibitory effect was not obtained at the sacrifice of regular movement. Collectively, these results indicated that injection of TRPV1 antagonist in nucleus accumbens is capable of attenuating persistent morphine conditioned place preference without affecting normal activity. Thus, TRPV1 antagonist is one of the promising therapeutic drugs for the treatment of opioid addiction.

The cognitive impairment of pituitary adenomas (PAs) has received increasing attention. Hyperprolactinemia and tumor mass effect are the potential causes. The aim of this study was to identify possible cognitive impairment and to further explore the correlation between these indices and prolactin (PRL) levels, based on the control of tumor size. Twenty-seven patients with prolactinomas (patient group) and twenty-six matched health control group (HC group) were enrolled in this study. All participants performed the flanker task while we continuously recorded electroencephalography data. On the behavioral performance level, patients showed a significantly slower reaction time (RT) in both flanker types. Concerning the event-related potentials level, patients elicited reduced P2 and enhanced N2 amplitudes compared with the HC group, suggesting an impairment of attentional processing (P2) and conflict monitoring (N2). Moreover, the patient group also induced lower P3 amplitudes relative to the HC group in both types, indicating that there were deficits in attentional resource allocation ability. We also found a significant correlation between the P3 amplitudes and incongruent condition RTs, as well as the subsequent PRL levels in the patient group. In conclusion, this is an innovative study that reveals the impaired cognition abilities in prolactinomas, and also proposes the possible cognitive toxicity of oversecreted PRL levels, which provides evidence for further research on the cognitive decline in PAs.