NMDA receptors in the lateral hypothalamus have an inhibitory influence on the tachycardiac response to acute restraint stress in rats

Abstract

The aim of the present study was to investigate the role of the lateral hypothalamus (LH) and its local glutamatergic neurotransmission in the cardiovascular adjustments observed when rats are submitted to acute restraint stress. Bilateral microinjection of the nonspecific synaptic inhibitor CoCl2 (0.1 nmol in 100 nL) into the LH enhanced the heart rate (HR) increase evoked by restraint stress without affecting the blood pressure increase. Local microinjection of the selective N-methyl-d-aspartate (NMDA) glutamate receptor antagonist LY235959 (2 nmol in 100 nL) into the LH caused effects that were similar to those of CoCl2 . No changes were observed in the restraint-related cardiovascular response after a local microinjection of the selective non-NMDA glutamatergic receptor antagonist NBQX (2 nmol in 100 nL) into the LH. Intravenous administration of the muscarinic cholinergic receptor antagonist homatropine methyl bromide (0.2 mg/kg), a quaternary ammonium drug that does not cross the blood-brain barrier, abolished the changes in cardiovascular responses to restraint stress following LH treatment with LY235959. In summary, our findings show that the LH plays an inhibitory role on the HR increase evoked by restraint stress. Present results also indicate that local NMDA glutamate receptors, through facilitation of cardiac parasympathetic activity, mediate the LH inhibitory influence on the cardiac response to acute restraint stress.

Chronic Desipramine Prevents Acute Stress-Induced Reorganization of Medial Prefrontal Cortex Architecture by Blocking Glutamate Vesicle Accumulation and Excitatory Synapse Increase

“…Control animals were kept in the stress apparatus for the same interval of time (40 minutes) without delivering the shocks. For the acute restraint (RS) stress, rats were immobilized in air-accessible cylinders for 1 hour ( Deolindo et al, 2013 ). Stress exposure was conducted between 8:00 am and 12:00 am in a room different from that used for housing.…”

Corticolimbic regulation of cardiovascular responses to stress

“…Briefly, tonic GABAergic signaling within the PH and neighboring dorsomedial hypothalamus constrains HR and arterial responses to stress and disinhibition of these nuclei increases reactivity [46,96,97]. The LHA inhibits tachycardic responses to stress via the parasympathetic nervous system [98], while the mPOA mediates stress effects of angiotensin on mean arterial pressure (MAP) and vascular resistance [99]. The PVH has multiple mechanisms for bi-directional control of HR and blood pressure responses [100,101], although net synaptic activity in the PVH facilitates cardiovascular stress responses [102].…”

Lateral hypothalamus involvement in control of stress response by bed nucleus of the stria terminalis endocannabinoid neurotransmission in male rats

“…Such as BSNT, the LH also plays a role in physiological and behavioral responses to emotional stress 2 , 21 – 24 . Regarding the stress-evoked cardiovascular responses, previous studies documented a role of this diencephalic region controlling cardiovascular responses evoked by both conditioned and unconditioned aversive stimuli 25 – 27 . The LH has an inhibitory influence in cardiovascular responses to unconditioned stress 27 , which is mediated by a balance of local excitatory and inhibitory inputs.…”

“…Regarding the stress-evoked cardiovascular responses, previous studies documented a role of this diencephalic region controlling cardiovascular responses evoked by both conditioned and unconditioned aversive stimuli 25 – 27 . The LH has an inhibitory influence in cardiovascular responses to unconditioned stress 27 , which is mediated by a balance of local excitatory and inhibitory inputs. Indeed, local LH treatment with a selective NMDA glutamatergic receptor antagonist enhanced the HR response to restraint stress 27 , whereas opposite effect was observed following LH treatment with a selective GABA A receptor antagonist 28 .…”