Evidence against the involvement of the nucleus tractus solitarii in the sympatholytic effect of 8-hydroxy-2-(di-n-propylamino)tetralin in the cat.
In different animal species, microinjections of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into the nucleus tractus solitarii failed to alter arterial blood pressure and sympathetic nerve activity; however, the cardiovascular effects (hypotension, bradycardia, reduction in sympathetic nerve activity) of intravenous administration of 8-OH-DPAT were significantly reduced after blockade of the nucleus tractus solitarii by kainic acid as well as after blockade of the lateral tegmental field by kainic acid. The aim of the present study was to clarify these conflicting results. In the anesthetized cat, inhibition of neurotransmission in the nucleus tractus solitarii by bilateral microinjections of either muscimol (1 nmol in 50 nl) or kynurenic acid (2.5 nmol in 50 nl) suppressed the baroreceptor reflex and abolished the synchronism between the renal sympathetic bursts; however, these procedures did not alter the dose-related hypotension, bradycardia and sympatho-inhibition elicited by cumulative doses of 8-OH-DPAT (1-30 micrograms/kg i.v.). Moreover complete electrolytic destruction of the nucleus tractus solitarii, assessed by a complete loss of the baroreceptor reflex and the cardiac-related bursts of the sympathetic nerves, failed to alter the inhibitory effects of i.v. 8-OH-DPAT. Bilateral microinjections of muscimol into the lateral tegmental field induced a decrease of mean arterial blood pressure, heart rate and renal nerve activity (by respectively -35 +/- 13 mm Hg, -30 +/- 16 beats/min and -53 +/- 14%) and greatly reduced the effects of subsequent i.v. administration of 8-OH-DPAT. The present data indicate that the nucleus tractus solitarii does not play a dominant role in the central action of 8-OH-DPAT whereas they confirm our previous results showing that the lateral tegmental field is involved in this action and in the mecanisms regulating sympathetic tone. The results also suggest that kainic acid lesions are not restricted to the region in which the neurotoxic agent is injected.
Vayssettes-Courchay
C
C
Servier Research Institute, Department of Angiology, Suresnes, France.
Bouysset
F
F
Verbeuren
T J
TJ
Laubie
M
M
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000633:toxicity; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D018755:GABA Agonists / Q000008:administration & dosage / Q000633:toxicity; D006339:Heart Rate / Q000187:drug effects; D007608:Kainic Acid / Q000008:administration & dosage / Q000633:toxicity; D007736:Kynurenic Acid / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D008845:Microinjections; D009118:Muscimol / Q000008:administration & dosage / Q000633:toxicity; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017552:Solitary Nucleus / Q000502:physiology*; D013565:Sympatholytics / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects; D013681:Tegmentum Mesencephali / Q000502:physiology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D017366:Serotonin Receptor Agonists; D013565:Sympatholytics; D009118:Muscimol; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007736:Kynurenic Acid; D007608:Kainic Acid