TY - JOUR
T1 - Electrophysiological and biochemical responses of noradrenergic neurons to a non-amphetamine CNS stimulant
AU - German, Dwight C.
AU - Sanghera, Manjit K.
AU - Sanford Kiser, R.
AU - McMillen, Brian A.
AU - Shore, Parkhurst A.
N1 - Funding Information:
This research was supported in part by USPHS Grants MH-27574 and MH-05831. The authors wish to thank Sally Browder, Robert Brown and Harold Harden for help with some of the electrophysiological studies, Margaret Mendershausen for the histological work, and Diana Corn for typing the manuscript.
PY - 1979/4/27
Y1 - 1979/4/27
N2 - Amfonelic acid (AFA), a potent non-amphetamine CNS stimulant, has been shown previously to have marked effects on dopamine (DA) metabolism and DA neuronal activity, but no effect on norepinephrine (NE) metabolism. AFA is known to inhibit the NE neuronal uptake mechanism. Other NE uptake inhibitors, such as desipramine (DMI), have been shown to decrease the firing rate of NE-containing locus coeruleus (LC) neurons. The purpose of the present study was to compare the actions of AFA and DMI electrophysiologically on LC neurons, and biochemically on NE metabolism in whole brain. The effects of the two drugs were similar in decreasing LC firing rate, with DMI being more potent. Brain NE metabolism was not influenced by either AFA or DMI at doses considerably higher than those which were effective in reducing NE neuronal impulse flow. Thus, NE uptake inhibition coupled with a decrease in impulse flow results in no net change in NE metabolite formation. The effects of AFA on LC unit activity do not seem to be due to its marked effects on brain DA, since DA receptor blockade with haloperidol had little effect on LC unit responsiveness to AFA (or amphetamine). Whereas AFA has dramatic effects on DA metabolism via enhanced release per impulse, the drug has minimal effects on NE metabolism, and this specificity of action may be related to differences in NE and DA transmitter storage mechanisms. It is concluded that the effects of AFA on NE neuronal firing rate are likely due to the drug's DMI-like action and not to enhanced NE release per impulse.
AB - Amfonelic acid (AFA), a potent non-amphetamine CNS stimulant, has been shown previously to have marked effects on dopamine (DA) metabolism and DA neuronal activity, but no effect on norepinephrine (NE) metabolism. AFA is known to inhibit the NE neuronal uptake mechanism. Other NE uptake inhibitors, such as desipramine (DMI), have been shown to decrease the firing rate of NE-containing locus coeruleus (LC) neurons. The purpose of the present study was to compare the actions of AFA and DMI electrophysiologically on LC neurons, and biochemically on NE metabolism in whole brain. The effects of the two drugs were similar in decreasing LC firing rate, with DMI being more potent. Brain NE metabolism was not influenced by either AFA or DMI at doses considerably higher than those which were effective in reducing NE neuronal impulse flow. Thus, NE uptake inhibition coupled with a decrease in impulse flow results in no net change in NE metabolite formation. The effects of AFA on LC unit activity do not seem to be due to its marked effects on brain DA, since DA receptor blockade with haloperidol had little effect on LC unit responsiveness to AFA (or amphetamine). Whereas AFA has dramatic effects on DA metabolism via enhanced release per impulse, the drug has minimal effects on NE metabolism, and this specificity of action may be related to differences in NE and DA transmitter storage mechanisms. It is concluded that the effects of AFA on NE neuronal firing rate are likely due to the drug's DMI-like action and not to enhanced NE release per impulse.
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U2 - 10.1016/0006-8993(79)90218-X
DO - 10.1016/0006-8993(79)90218-X
M3 - Article
C2 - 427592
AN - SCOPUS:0018394656
SN - 0006-8993
VL - 166
SP - 331
EP - 339
JO - Brain Research
JF - Brain Research
IS - 2
ER -