Deep brain stimulation of the subthalamic nucleus (DBS-STN) is an effective treatment for advanced motor symptoms of Parkinson’s disease (PD). Recently, a connection between the limbic part of the STN and side effects of DBS-STN has been increasingly recognized. Animal studies have shown that DBS-STN influences behavior and provokes neurochemical changes in regions of the limbic system. Some of these regions, which are activated during DBS-STN, are involved in neuroimmunomodulation. The therapeutic effects of DBS-STN in PD treatment are clear, but the influence of DBS-STN on peripheral immunity has not been reported so far. In this study, we examined the effects of unilateral DBS-STN applied in male Wistar rats with 6-hydroxydopamine PD model (DBS-6OHDA) and rats without nigral dopamine depletion (DBS) on corticosterone (CORT) plasma concentration, blood natural killer cell cytotoxicity (NKCC), leukocyte numbers, lymphocyte population and apoptosis numbers, plasma interferon gamma (IFN-γ), interleukin 6 (IL-6), and tumor necrosis factor (TNF-α) concentration. The same peripheral immune parameters we measured also in non-stimulated rats with PD model (6OHDA). We observed peripheral immunity changes related to PD model. The NKCC and percentage of T cytotoxic lymphocytes were enhanced, while the level of lymphocyte apoptosis was down regulated in 6OHDA and DBS-6OHDA groups. After DBS-STN (DBS-6OHDA and DBS groups), the plasma CORT and TNF-α were elevated, the number of NK cells and percentage of apoptosis were increased, while the number of B lymphocytes was decreased. We also found, changes in plasma IFN-γ and IL-6 levels in all the groups. These results suggest potential peripheral immunomodulative effects of DBS-STN in the rat model of PD. However, further studies are necessary to explain these findings and their clinical implication.

The pedunculopontine tegmental nucleus (PPN) regulates the activity of dopaminergic cells in the ventral tegmental area (VTA). In this study, the role of opioid receptors (OR) in the PPN on motivated behaviors was investigated by using a model of feeding induced by electrical VTA-stimulation (Es-VTA) in rats (male Wistar; n = 91). We found that the OR excitation by morphine and their blocking by naloxone within the PPN caused a change in the analyzed motivational behavior and neuronal activation. The opioid injections into the PPN resulted in a marked, dose-dependent increase/decrease in latency to feeding response (FR), which corresponded with increased neuronal activity (c-Fos protein), in most of the analyzed brain structures. Morphine dosed at 1.25/1.5 µg into the PPN significantly reduced behavior induced by Es-VTA, whereas morphine dosed at 0.25/0.5 µg into the PPN did not affect this behavior. The opposite effect was observed after the naloxone injection into the PPN, where its lowest doses of 2.5/5.0 μg shortened the FR latency. However, its highest dose of 25.0 μg into the PPN nucleus did not cause FR latency changes. In conclusion, the level of OR arousal in the PPN can modulate the activity of the reward system.

Amphetamine abuse is a global health epidemic that is difficult to treat due to individual differences in response to environmental factors, including stress reactivity and anxiety levels, as well as individual neuronal differences, which may result in increased/decreased vulnerability to addiction. In the present study, we investigated whether the Wistar rats behavioral traits of high (HR) and low (LR) locomotor activity to novelty influence motivational behavior (induced feeding model; iFR by electrical stimulation of the ventral tegmental area; Es-VTA) supported by amphetamine injection into the nucleus accumbens shell (AcbSh) (HR_Amph, n = 5; LR_Amph, n = 5). A correlation was found between the novelty test’s locomotor activity score and the frequency threshold percentage change (p < 0.001, Rs = −0.867). In HR_Amph, there was a shortening (−24.16%), while in LR_Amph, there was a lengthening (+51.84%) of iFR latency. Immunofluorescence studies showed differential neuronal density (activity of tyrosine hydroxylase, choline acetyltransferase, and cFos protein) in the selected brain structures in HR_Amph and LR_Amph animals as well as in comparison to a control group (HR_ACSF, n = 5; LR_ACSF, n = 5). These results contribute to expanding the state of knowledge of the behavioral and neuronal propensity to take drug abuse.

Serotonin (5–HT) in the brain is involved in the regulation of various emotional states and behaviors. Most serotonergic neurons are located in the raphe nuclei. The raphe magnus (RMg) is one of the raphe nuclei and belongs to the caudal raphe complex. The primary goal of our research was to examine the effects of chronic, repeated electrical stimulation of the RMg on rats’ motility over a period of 15 days. During the research, 35 rats were used; 21 rats underwent electrical stimulation of the RMg (RMg-ST), while 14 rats were included in the control group (RMg-Sham). In addition, we aimed to evaluate the effects of electrical stimulation in the RMg-ST group as well as the naïve procedure in the RMg-Sham group on anxiety-related behaviors and spatial memory on selected days 30 min after the end of stimulation. We found that rats in the RMg-ST group were characterized by considerably higher locomotor activity than animals in the RMg-Sham group over a 15-day stimulation period. Stimulated animals were less anxious during the elevated plus maze on the 4th and 5th days of stimulation and demonstrated improved memory performance during the Morris water maze conducted between the 9th and 12th days of stimulation in comparison to the control animals. Furthermore, in both behavioral tests, rats’ motility when subjected to the RMg electrical stimulation was much higher than in control rats. On the last day of the 15-day stimulation period, rats were sacrificed, and their brains were collected. Brain immunofluorescent analysis revealed an increase in the number of 5–HT-positive cells in the RMg-ST group and altered activity of c-Fos-positive cells in selected brain structures connected with locomotion (secondary motor cortex), anxiety (arcuate nucleus of the hypothalamus), and spatial memory (dentate gyrus) after stimulation in comparison to the results in the RMg-Sham group. These findings suggest that locomotion may be strictly dependent on the RMg neuronal projections, and electrical stimulation of the structure influences cognitive behaviors.