The bradycardic and hypotensive responses to serotonin are reduced by activation of GABA A receptors in the nucleus tractus solitarius of awake rats

Abstract

We investigated the effects of bilateral injections of the GABA receptor agonists muscimol (GABA A ) and baclofen (GABA B ) into the nucleus tractus solitarius (NTS) on the bradycardia and hypotension induced by iv serotonin injections (5-HT, 2 µg/rat) in awake male Holtzman rats. 5-HT was injected in rats with stainless steel cannulas implanted bilaterally in the NTS, before and 5, 15, and 60 min after bilateral injections of muscimol or baclofen into the NTS. The responses to 5-HT were tested before and after the injection of atropine methyl bromide. Muscimol (50 pmol/50 nl, N = 8) into the NTS increased basal mean arterial pressure (MAP) from 115 ± 4 to 144 ± 6 mmHg, did not change basal heart rate (HR) and reduced the bradycardia (-40 ± 14 and -73 ± 26 bpm at 5 and 15 min, respectively, vs -180 ± 20 bpm for the control) and hypotension (-11 ± 4 and -14 ± 4 mmHg, vs -40 ± 9 mmHg for the control) elicited by 5-HT. Baclofen (12.5 pmol/50 nl, N = 7) into the NTS also increased basal MAP, but did not change basal HR, bradycardia or hypotension in response to 5-HT injections. Atropine methyl bromide (1 mg/kg body weight) injected iv reduced the bradycardic and hypotensive responses to 5-HT injections. The stimulation of GABA A receptors in the NTS of awake rats elicits a significant increase in basal MAP and decreases the cardiac Bezold-Jarisch reflex responses to iv 5-HT injections. Correspondence

Neuroanatomic relationships between the GABAergic and serotonergic systems in the developing human medulla

“…The most striking findings in the development of the two systems relative to one another are in the raphé obscurus in which there is an increase in GABA Aα3 expression and decrease in GABA Aα1 expression over the same time-period, suggesting a dynamic period in the GABAergic development in a site heavily concentrated with 5-HT neurons. The raphé obscurus is implicated in respiratory control (Feldman et al, 2006; Pierrefiche et al, 1998; Shao et al, 1997), carbon dioxide chemosensitivity (Curran et al, 2000; Curran et al, 2001; Nattie, 1999; Nattie, 1991), heart rate and blood pressure regulation (Dampney, 1994; Heesch et al, 2006; Menezes et al, 2007), baroreflexes (Callera et al, 2000; Callera et al, 2005), temperature control (Darnall et al, 2001; Darnall et al, 2006), and pain (Stamford, 1995). Our studies suggest that the development of 5-HT markers is “static” in the raphé obscurus from birth into infancy, yet changes continue to occur in GABA A receptor subunits; thus, potential developmental changes in 5-HT-mediated function in the raphé obscurus after birth may reflect, at least in part, changes in GABA modulation.…”

Cardiovascular Autonomic Responses in the VCD Rat Model of Menopause: Effects of Short- and Long-Term Ovarian Failure

“…Although the chemoreflex induces an increased sympathetic activity, leading to increased arterial pressure, 21 the Bezold-Jarish reflex induces parasympathetic activation concomitant to sympathetic inhibition, leading to bradycardia and hypotension. 22 Not only the exacerbated response to sympathetic excitation but also a reduced response to sympathetic inhibition can lead to hypertension in the long term. However, alterations in both reflexes are poorly understood during menopause progression.…”