TONIC GLUTAMATE NEUROTRANSMISSION BY NMDA RECEPTORS IN PARAVENTRICULAR NUCLEUS IS INCREASED IN CONSCIOUS RATS INDUCED TO 6-OHDA PARKINSONISM

Parkinson's disease (PD) is a progressive neurodegenerative disease that manifests itself clinically after reaching an advanced pathological stage. In addition to the motor signals, PD patients present cardiovascular changes that appear to be accompanied by alterations in the autonomic nervous system. Recent data have shown that rats induced to Parkinsonism through bilateral administration of 6‐hydroxydopamine (6‐OHDA) in the substantia nigra pars compacta (SNpc) showed lower mean arterial pressure (MAP) and heart rate (HR) compared to their controls, as reduction in sympathetic modulation. The paraventricular nucleus of the hypothalamus (PVN) is an important structure for the integration of autonomic function and blood pressure (BP) control in the different behavioral and pathological situations. Thus, the aim of this study was to evaluate the role of PVN excitatory pathways in the cardiovascular and autonomic regulation during Parkinsonism induced by 6‐OHDA. Male Wistar rats were anesthetized and two guide cannulas were implanted into the PVN. 6‐OHDA or sterile saline was bilaterally administered directly into the SNpc. After 6 days and twenty‐four hours before the experiments, the animals were anesthetized and a polyethylene catheter was inserted into the abdominal aorta through the femoral artery and externalized dorsally to record MAP and HR in the conscious state. Administration of bicuculline (gaba A antagonist) in the PVN in sham group promoted an increase in MAP (Bic: 123 ± 7, baseline: 109 ± 5 mmHg) and HR (Bic: 435 ± 22, baseline: 355 ± 11 bpm). In the 6‐OHDA group, bicuculline exacerbated the increases in MAP and HR observed (MAP, 136 ± 3 mmHg; FC, 487 ± 8 bpm). Additionally, NBQX (non‐NMDA receptor inhibitor) did not promote changes in MAP and HR of the sham group, just as in 6‐OHDA group. On the other hand, microinjection of LY235959 (inhibitor of NMDA glutamate receptor) in the PVN of the sham group did not promote cardiovascular alterations, but in the 6‐OHDA group there was a decrease in MAP (LY: 83 ± 4, baseline: 98 ± 5 mmHg) and HR (LY: 251 ± 12, Baseline: 310 ± 14 bpm). Confirmation of 6‐OHDA lesion was observed by decreased levels (at least 70%) of dopamine in striatum. Our data suggest a role of NMDA receptors in the PVN, on tonic cardiovascular control of 6‐OHDA Parkinsonism in rats. Support or Funding Information Fundação Araucária; Capes (fellowship to EDTA); CNPq (Research fellowship to MCMP and CCC) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .