Noradrenergic responses in rat hippocampus: evidence for medication by alpha and beta receptors in the in vitro slice.
The effect of perfused norepinephrine (NE) on evoked potentials in CA1 of the in vitro rat hippocampus was examined. Weak and variable effects on population spike amplitude were observed, with lower doses of NE generally producing excitations and higher doses more often producing inhibitions. Clonidine, an alpha-receptor agonist, produced a dose-dependent inhibition of population spike amplitude; this inhibition was effectively antagonized by the alpha-antagonist, phentolamine. Isoproterenol (ISO), a beta-agonist, produced marked increases in population spike amplitude which could be antagonized by timolol, a beta-receptor antagonist. Phentolamine did not antagonize the excitations produced by ISO, and timolol had no effect on the inhibitions seen with clonidine. After pretreatment with either phentolamine or timolol, NE perfusion elicited robust and consistent elevations or reductions in the population spike, respectively. A potent cyclic AMP derivative, 8-p-chlorophenylthio cyclic AMP, produced large increases in population spike amplitude which appeared similar to the responses seen with beta-agonists. No changes in field EPSP amplitudes were observed with any of the drugs tested. Taken together, these results suggest that NE may interact with alpha-adrenergic receptors to decrease pyramidal cell excitability, and the beta-adrenergic receptors to increase pyramidal cell excitability; the beta-effect may involve cAMP.
D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D046508:Culture Techniques; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013873:Thionucleotides / Q000494:pharmacology; D013999:Timolol / Q000494:pharmacology
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D013873:Thionucleotides; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D013999:Timolol; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol; D003000:Clonidine; D009638:Norepinephrine; D010646:Phentolamine