GABAA and excitatory amino acid receptors in dorsomedial hypothalamus and heart rate in rats.
We have previously shown that microinjection of drugs that interfere with the function of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) into the hypothalamus produces cardiorespiratory and behavioral changes resembling those seen in emotional stress. The purpose of this study was to determine whether excitatory amino acids (EAAs) can produce a cardiovascular response similar to that caused by the GABAA receptor antagonist bicuculline methiodide (BMI) when microinjected at the same hypothalamic site in urethan-anesthetized rats and to clarify the precise locus of action of these agents. N-methyl-D-aspartic acid (NMDA, 0.68-6.8 pmol/50 nl) and kainic acid (KA, 0.47-4.7 pmol/50 nl) produced dose-related increases in heart rate and blood pressure when injected at sites in the dorsomedial hypothalamus reactive to BMI (20 pmol/50 nl). Higher doses of NMDA (68 pmol), however, failed to elicit consistent increases in heart rate and blood pressure when injected at these same sites. The effects of NMDA were selectively blocked by the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid, whereas the effects of KA were selectively blocked by the non-NMDA EAA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. These results demonstrate that 1) blockade of inhibitory amino acid receptors or stimulation of EAA receptors in the dorsomedial nucleus of the hypothalamus produces tachycardic and pressor responses in urethan-anesthetized rats and 2) use of high doses of EAAs may be an unreliable method of evoking local neuronal excitation in certain regions of the central nervous system.
Soltis
R P
RP
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis 46202.
DiMicco
J A
JA
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D016202:N-Methylaspartate / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D011810:Quinoxalines; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D007608:Kainic Acid; D001640:Bicuculline