Hippocampal noradrenergic responses in vivo and in vitro. Characterization of alpha and beta components.
Pressure ejection of l-norepinephrine (NE) in the in vivo rat hippocampus generally produced depression of pyramidal cell spontaneous activity. In addition, both excitation and biphasic responses were observed. NE-induced inhibition of firing rate was effectively antagonized by concurrent administration of the alpha antagonist phentolamine, but was largely unaltered by the beta antagonist timolol. On the other hand, NE-induced elevation in spontaneous firing rate was effectively blocked by timolol, and largely unaffected by phentolamine. Another beta antagonist, sotalol, did not selectively antagonize either NE-induced inhibition or NE-induced excitation. The beta agonist 2-fluoro-NE produced increases in pyramidal cell firing rates in most cells studied, while the alpha agonist 6-fluoro-NE inhibited the majority of cells examined. The effects of sotalol were also examined on alpha and beta receptor-mediated field responses in the in vitro hippocampal slice. Sotalol was shown to be a selective beta antagonist in this system, blocking excitation evoked by the beta agonist isoproterenol while having no effect on inhibition elicited by the alpha agonist clonidine; however, the potency of sotalol (Ki = 3.5 microM) was considerably less than that of timolol (Ki = 50 nM). Taken together, these results suggest that NE-induced depression and elevation in hippocampal pyramidal cell spontaneous discharge in vivo are mediated via alpha and beta adrenoceptors, respectively.
D000818:Animals; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013015:Sotalol / Q000494:pharmacology; D013999:Timolol / Q000494:pharmacology
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D013999:Timolol; D013015:Sotalol; D009638:Norepinephrine; D010646:Phentolamine