Blockade of NMDA Receptors in the Dorsomedial Hypothalamic Region Attenuates the Cardiovascular Response Evoked by Cage Switch Stress

Abstract

Evidence indicates that the dorsomedial hypothalamic region (DMH) plays a key role in the organization of the cardiovascular (CV) response to acute emotional stress. Inhibition of DMH and/or blockade of excitatory amino acid (EAA) receptors in this region attenuate the physiological responses evoked by stress. However, all these effects have been explored in a single stress model (air‐stress). We evaluate the contribution of NMDA receptors in the DMH on the CV response evoked by cage switch stress (CS stress). Under anesthesia (tribromoethanol, 250 mg/kg), Wistar rats received guide cannulas into DMH. Seven days after, a cannula was inserted into femoral artery for HR and BP recording. After 24 hs, bilateral nanoinjections (100nL) of vehicle (saline 0.9%, n=7), the GABAA agonist muscimol (100pmol, n=8) or the NMDA antagonist AP‐5 (100pmol, n=6) were performed into DMH; ten min later, rats were submitted to CS stress. An additional control group was also tested (no injection, intact group, n=9). In the intact group and in the vehicle group CS stress evoked a tachycardic response (Δ 119±12 bpm and 121±11 bpm) accompanied by large increases in BP (Δ 60±2 mmHg and Δ 60±3 bpm, respectively). The tachycardic and pressor responses were markedly reduced by muscimol and AP‐5 (musc: ΔHR: 62±7 bpm and Δ MAP: 37±4 mmHg; AP‐5: Δ HR: 31±7 bpm and Δ MAP: 39±3 mmHg, P<0.05 vs. vehicle). Corticosterone and glucose levels were unaffected by CS or any treatment. Data suggest that the DMH is also important for controlling CV responses in other forms of acute emotional stress. Part of this response involves activation of NMDA EAA receptors. Support: Fapemig, Capes, CNPq