Focal electrical stimulation on an alcohol disorder model using magnetic resonance imaging-compatible chronic neural monopolar carbon fiber electrodes.

Neuromodulation interventions, such as Deep Brain Stimulation (DBS) and repeated transcranial magnetic stimulation (rTMS), are proposed as possible new complementary therapies to treat substance use disorders (SUD) such as alcohol use disorder (AUD). It is hypothesized that neuromodulation may induce neural plasticity in the reward and frontostriatal systems via electrical field induction, possibly reducing symptoms. Preclinical self-administration rodent models of AUD may help us gain insight into the effects of neuromodulation therapies on different pathology, as well as the neural mechanisms behind the positive effects. DBS, or any type of brain stimulation using intracranial electrodes in rodents, would benefit from the use of magnetic resonance imaging (MRI) to study the longitudinal effects and mechanisms of stimulation as well as novel targets, as it is a non-invasive technique that allows the analysis of structural and functional changes in the brain. To do this, there is a need for MRI-compatible electrodes that allow for MRI acquisition with minimal distortion of the magnetic field. In this protocol, we present a method for the construction and surgery of chronically implantable monopolar carbon electrodes for use in rats. Unlike conventional electrodes, carbon electrodes are resistant to high temperatures, flexible, and generate fewer artifacts in MRI compared to conventional ones. We validated its use by using a focal electrical stimulation high-frequency (20 Hz) protocol that lasted ∼10 sessions. We propose that this technique can also be used for the research of the neurophysiological bases of the neuromodulatory treatment in other preclinical substance use disorders (SUD) models.

Hypothalamic paraventricular nucleus stimulation enhances c-Fos expression in spinal and supraspinal structures related to pain modulation.

The hypothalamic paraventricular nuclei (PVN) inhibits spinal nociception. Furthermore, projections from the PVN to other structures related to pain modulation exist, but a functional interaction has not yet been fully demonstrated. As an initial approach, we show here that PVN electric stimulation with the same parameters used to induce analgesia in rats enhances c-Fos expression not only in the dorsal horn of the spinal cord but also in the nucleus raphe magnus, locus coeruleus and the periaqueductal gray area. These results suggest that a functional interaction between these structures could occur, possibly to assure a mechanism of endogenous analgesia.

The hormone prolactin is a novel, endogenous trophic factor able to regulate reactive glia and to limit retinal degeneration.

Retinal degeneration is characterized by the progressive destruction of retinal cells, causing the deterioration and eventual loss of vision. We explored whether the hormone prolactin provides trophic support to retinal cells, thus protecting the retina from degenerative pressure. Inducing hyperprolactinemia limited photoreceptor apoptosis, gliosis, and changes in neurotrophin expression, and it preserved the photoresponse in the phototoxicity model of retinal degeneration, in which continuous exposure of rats to bright light leads to retinal cell death and retinal dysfunction. In this model, the expression levels of prolactin receptors in the retina were upregulated. Moreover, retinas from prolactin receptor-deficient mice exhibited photoresponsive dysfunction and gliosis that correlated with decreased levels of retinal bFGF, GDNF, and BDNF. Collectively, these data unveiled prolactin as a retinal trophic factor that may regulate glial-neuronal cell interactions and is a potential therapeutic molecule against retinal degeneration.