5-HT1A agonists uncouple noradrenergic somatodendritic impulse flow and terminal release.
Both noradrenergic (NE) and serotonergic (5-HT) systems have been implicated in anxiety and depression, as well as in the therapeutic actions of drugs treating these conditions. We have used microelectrode recordings of nerve cell impulse frequencies and in vivo voltammetric recordings of monoamine release to evaluate effects of the arylpiperazine 5-HT1A anxiolytics, buspirone and ipsapirone. Both buspirone and ipsapirone significantly depressed 5-HT neuronal firing rates in dorsal raphe (DR), but significantly increased NE neuronal firing rates in locus coeruleus (LC). In CA1 region of hippocampus, both buspirone and ipsapirone significantly depressed NE release with potencies greater than those required for the significant depression of 5-HT release. It is concluded that, contrary to the belief that the 5-HT1A arylpiperazines act primarily through 5-HT mechanisms, alterations in NE function may be critically important for their therapeutic effects, just as is the case for the benzodiazepine anxiolytics and the tricyclic antidepressants.
Department of Pharmacology, City University of New York Medical School, NY.
P A
PA
Broderick
M F
MF
Piercey
D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D002065:Buspirone / Q000494:pharmacology*; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008125:Locus Coeruleus / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D011743:Pyrimidines; D012701:Serotonin; C043077:ipsapirone; D002065:Buspirone; D009638:Norepinephrine