Behavioral and Autonomic Responses to Acute Restraint Stress Are Segregated within the Lateral Septal Area of Rats

Background: The Lateral Septal Area (LSA) is involved with autonomic and behavior responses associated to stress. In rats, acute restraint (RS) is an unavoidable stress situation that causes autonomic (body temperature, mean arterial pressure (MAP) and heart rate (HR) increases) and behavioral (increased anxiety-like behavior) changes in rats. The LSA is one of several brain regions that have been involved in stress responses. The aim of the present study was to investigate if the neurotransmission blockade in the LSA would interfere in the autonomic and behavioral changes induced by RS. Methodology/Principal Findings: Male Wistar rats with bilateral cannulae aimed at the LSA, an intra-abdominal datalogger (for recording internal body temperature), and an implanted catheter into the femoral artery (for recording and cardiovascular parameters) were used. They received bilateral microinjections of the non-selective synapse blocker cobalt chloride (CoCl2, 1 mM / 100 nL) or vehicle 10 min before RS session. The tail temperature was measured by an infrared thermal imager during the session. Twenty-four h after the RS session the rats were tested in the elevated plus maze (EPM). Conclusions/Significance: Inhibition of LSA neurotransmission reduced the MAP and HR increases observed during RS. However, no changes were observed in the decrease in skin temperature and increase in internal body temperature observed during this period. Also, LSA inhibition did not change the anxiogenic effect induced by RS observed 24 h later in the EPM. The present results suggest that LSA neurotransmission is involved in the cardiovascular but not the temperatur

Role of ventrolateral medulla in reflex cardiovascular responses to activation of skin and muscle nerves

Central neuronal circuits mediating reflex cardiovascular responses to skin and muscle nerve stimulation were studied in rats under urethan anesthesia. Responses of right rostral ventrolateral medulla (RVLM) and caudal ventrolateral medulla (CVLM) cardiovascular neurons to stimulation of contralateral skin and muscle afferent fibers were investigated. Stimulation of the tibial (muscle) nerve excited 19 (86%) of 22 CVLM neurons and inhibited 18 (82%) of 22 RVLM neurons. Stimulation of the sural (skin) nerve excited 20 (91%) of the 22 RVLM neurons but did not affect the firing rate of any of the 22 CVLM neurons. Electrolytic lesions of the CVLM abolished the depressor responses induced by stimulation of the tibial nerve without affecting the pressor response caused by sural nerve stimulation. Similarly, reversible blockade of the CVLM by microinjection of gamma-amino-butyric acid or CoCl2 abolished the depressor response to stimulation of the tibial nerve without affecting the pressor response induced by sural nerve stimulation. These results suggest that vasodepressor responses to muscle nerve activation are mediated by a neuronal inhibitory pathway to the RVLM relayed through the CVL

Neuronal and cardiovascular responses to ANF microinjected into the solitary nucleus

The effect on single-unit activity, arterial pressure, and heart rate of a microinjection of atrial natriuretic factor (ANF) into 78 histologically verified sites in the nucleus tractus solitarii (NTS) was investigated in rats. Injections of 50 nl of 10(-7) M ANF excited 34 neurons (44%), mainly localized at the level of the obex, inhibited 15 (19%), and had no effect on the remaining 29 (37%). The increase in firing frequency of the 34 excited neurons was always followed by a decline in mean arterial pressure [MAP, -10.6 +/- 1.8 (SE) mmHg; P less than 0.01] and heart rate [HR, -9.6 +/- 3.1 (SE) beats/min; P less than 0.05]. When injections of ANF caused either no effect or inhibition of single-unit activity, no changes in either MAP or HR were observed. Single units excited by injections of ANF were also excited by activation of arterial baroreceptors and inhibited by baroreceptor unloading. Control injections of an inactive peptide analogue of ANF or of vehicle never produced any effects on neuronal firing frequency or on MAP and HR. Similar results were obtained from animals paralyzed and artificially ventilated. These results support the hypothesis that ANF plays a role in the chemical transmission of baroreceptor information within the NT

Neuronal and cardiovascular responses to ANF microinjected into nucleus ambiguous

Effects of microinjection of atrial natriuretic factor (ANF) into cardioinhibitory sites in the nucleus ambiguous (NA) or on single vagal cardioinhibitory neurons (VCN) were investigated in urethan-anesthetized rats. Sites containing cardioinhibitory neurons were identified by observing a marked and reproducible bradycardia in response to microiontophoretically applied (20-40 nA) or microinjected (20 nl) 0.1 M L-glutamate. In 35 of the 40 (87.5%) cardioinhibitory sites identified by microinjection of glutamate, ANF (20 nl of 10(-7) M) decreased heart rate (HR; -47.1 +/- 2.5 beats/min). No responses were elicited in the other five sites. In animals paralyzed and artificially ventilated, the HR effects of ANF were not significantly different before and after muscle paralysis. Microinjections of 10 nl of 10(-7) M ANF caused excitation of 19 of 21 VCN (90%), which was followed by a decrease in HR (-20.8 +/- 2.3 beats/min); no neuronal or cardiovascular responses were elicited by ANF in the remaining two VCN. Bilateral vagotomy or atropine sulfate (1 mg/kg iv) abolished cardiac slowing without affecting neuronal activation, whereas propranolol (2 mg/kg iv) did not affect either response to ANF. These results suggest that ANF is a neuromediator involved in the excitation of cardioinhibitory neurons in the NA