Noradrenergic responses in rat hippocampus: electrophysiological actions of direct- and indirect-acting sympathomimetics in the in vitro slice.
The effects of perfusion of postulated direct- and indirect-acting sympathomimetics on evoked potentials in the CA1 region of the in vitro rat hippocampus were examined. A selective alpha agonist, 6-fluoronorepinephrine, produced depressions of population spike amplitude which were antagonized by the alpha antagonist phentolamine, but not by the beta antagonist timolol. The selective beta agonist, 2-fluoronorepinephrine, produced increases in population spike amplitude which were antagonized by timolol but not by phentolamine. Weak and variable responses were seen to the indirect-acting sympathomimetic tyramine, with lower doses producing increases and higher doses producing decreases in population spike amplitude, respectively. As with 2-fluoronorepinephrine, increases in spike amplitude elicited by tyramine were blocked by timolol but not by phentolamine. Another indirect-acting sympathomimetic, d-amphetamine, produced only increases in population spike amplitude which were blocked by timolol. Phencyclidine, an agent which may produce some of its central effects via noradrenergic synapses, was virtually ineffective in producing catecholamine-like responses in this system. Only nonspecific, local anesthetic effects were observed. Taken together with previous studies, these results support the hypothesis that activation of alpha and beta receptors decreases and increases, respectively, pyramidal cell excitability. Furthermore, although both alpha and beta receptors appear to be capable of interacting with endogenously released norepinephrine, the beta response may predominate.
D000200:Action Potentials / Q000187:drug effects; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D003913:Dextroamphetamine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013566:Sympathomimetics / Q000494:pharmacology*; D014439:Tyramine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D013566:Sympathomimetics; C036590:1-(1-phenylcyclohexyl)-3-methylpiperidine; C024882:3-fluoronorepinephrine; C024884:6-fluoronorepinephrine; D010622:Phencyclidine; D003913:Dextroamphetamine; D009638:Norepinephrine; D014439:Tyramine