Behavioral Reaction and c-fos Expression after Opioids Injection into the Pedunculopontine Tegmental Nucleus and Electrical Stimulation of the Ventral Tegmental Area.

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.

NMDA receptor modulation of the pedunculopontine tegmental nucleus underlies the motivational drive for feeding induced by midbrain dopaminergic neurons.

The mesolimbic system, particularly the somatodendritic ventral tegmental area (VTA), is responsible for the positive reinforcing aspects of various homeostatic stimuli. In turn, the pedunculopontine tegmental nucleus (PPN) is anatomically and functionally connected with the VTA and substantia nigra (SN). In the present study, we investigated the role of glutamate receptors in the PPN in motivated behaviors by using a model of feeding induced by electrical stimulation of the VTA in male Wistar rats (n = 80). We found that injection of 2.5/5 µg dizocilpine (MK-801; NMDA receptor antagonist) to the PPN significantly reduced the feeding response induced by unilateral VTA-stimulation. This reaction was significantly impaired after local injection of MK-801 into the PPN in the ipsilateral rather than the contralateral hemisphere. After NMDA injection (2/3 µg) to the PPN we did not observe behavioral changes, only a trend of a lengthening/shortening of the latency to a feeding reaction at the highest dose of NMDA (3 µg). Immunohistochemical TH+/c-Fos+ analysis revealed a decrease in the number of TH+ cells in the midbrain (VTA-SN) in all experimental groups and altered activity of c-Fos+ neurons in selected brain structures depending on drug type (MK-801/NMDA) and injection site (ipsi-/contralateral hemisphere). Additionally, the pattern of TH+/c-Fos+ expression showed lateralization of feeding circuit functional connectivity. We conclude that the level of NMDA receptor arousal in the PPN regulates the activity of the midbrain dopaminergic cells, and the PPN-VTA circuit may be important in the regulation of motivational aspects of food intake.