Noradrenergic depression of synaptic responses in hippocampus of rat: evidence for mediation by alpha 1-receptors.
Norepinephrine (NE) has been shown to have a biphasic effect on evoked potentials in the CA1 region of the hippocampus of the rat in vitro, with a beta receptor mediating an increase and an alpha receptor eliciting a decrease in the amplitude of the population spike. The purpose of this study was to use selective alpha-adrenergic agonists and antagonists to determine the subtype of receptor mediating the depressant response of NE. The present investigations demonstrated that the selective alpha 1 agonist, phenylephrine (2-50 microM) elicited a dose-dependent depression of the amplitude of the population spike. Clonidine, a relatively selective alpha 2-agonist, also depressed the amplitude of the population spike, but only at concentrations (10 microM) that were inconsistent with a selective action upon alpha 2-receptors. Another alpha 2-agonist, alpha-methylnorepinephrine (100-400 nM) did not depress the amplitude of the population spike. The depressant effect of NE was antagonized by the nonselective alpha antagonist, phentolamine (0.5-50 microM) and the alpha 1-selective antagonist, prazosin (1 microM), but not by the alpha 2-selective antagonist, idazoxan (1-10 microM). Phentolamine and prazosin antagonized the response to phenylephrine but not to clonidine. The depressant effect of NE was not antagonized by the antagonist of serotonin and dopamine, spiperone (100 nM); conversely, the effect of 8-hydroxy-2-(di-n-propylamine) tetralin (50 microM), a 5-HT1A receptor-selective agonist, which also depresses the amplitude of the population spike, was not antagonized by phentolamine (5 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
Mynlieff
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M
Department of Pharmacology, University of Colorado Medical Center, Denver 80262.
Dunwiddie
T V
TV
D000818:Animals; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D011942:Receptors, Adrenergic, alpha; D009638:Norepinephrine