Section 6
Chapter 5,342

Electro physiological and biochemical responses of noradrenergic neurons to a nonamphetamine central nervous system stimulant

German, S.C.; Sanghera, M.K.; Kiser, R.S.; Mcmillen, B.A.; Shore, P.A.

Brain Research 166(2): 331-340


ISSN/ISBN: 0006-8993
Accession: 005341979

Amfonelic acid (AFA), a potent non-amphetamine CNS stimulant, has marked effects on dopamine (DA) metabolism and DA neuronal activity, but no effect on norepinephrine (NE) metabolism. AFA inhibited the NE neuronal uptake mechanism. Other NE uptake inhibitors, such as desipramine (DMI), decrease the firing rate of NE-containing locus coeruleus (LC) neurons. The actions of AFA and DMI were compared electrophysiologically on LC neurons, and biochemically on NE metabolism in whole brain [in rats]. The 2 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. NE uptake inhibition coupled with a decrease in impulse flow resulted in no net change in NE metabolite formation. The effects of AFA on LC unit activity did 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. The effects of AFA on NE neuronal firing rate were likely due to the drug's DMI-like action and not to enhanced NE release per impulse.

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