Microinjection of muscimol into raphe pallidus suppresses tachycardia associated with air stress in conscious rats.
Sympathetically mediated tachycardia is a characteristic feature of the physiological response to emotional or psychological stress in mammals. Activation of neurons in the region of the dorsomedial hypothalamus appears to play a key role in the integration of this response. Tachycardia evoked by chemical stimulation of the dorsomedial hypothalamus can be suppressed by microinjection of the GABA(A) receptor agonist and neuronal inhibitor muscimol into the raphe pallidus (RP). Therefore, we tested the hypothesis that neuronal excitation in the RP mediates tachycardia seen in experimental air stress in rats. Microinjection of the GABA(A) receptor antagonist bicuculline methiodide (BMI) into the RP evoked increases in heart rate. At the same sites, microinjection of muscimol (80 pmol (100 nl)(-1)) had no effect on heart rate under baseline conditions but virtually abolished air stress-induced tachycardia, while microinjection of lower doses (10 or 20 pmol) produced transient but clear suppression. Microinjection of muscimol at sites outside the RP had no effect on stress-induced tachycardia, although modest suppression was apparent after injection at two sites within 500 microm of the RP. In another series of experiments, microinjection of muscimol (80 pmol (100 nl)(-1)) into the RP failed to influence the changes in heart rate produced by baroreceptor loading or unloading. These findings indicate that activity of neurons in the RP plays a previously unrecognized role in the generation of stress-induced tachycardia.
Zaretsky
Dmitry V
DV
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Zaretskaia
Maria V
MV
Samuels
Brian C
BC
Cluxton
Laura K
LK
DiMicco
Joseph A
JA
D000388:Air; D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D018755:GABA Agonists / Q000008:administration & dosage*; D008297:Male; D008845:Microinjections; D009118:Muscimol / Q000008:administration & dosage*; D011903:Raphe Nuclei / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000150:complications*; D013610:Tachycardia / Q000188:drug therapy* / Q000209:etiology*
D018755:GABA Agonists; D009118:Muscimol