Rate-independent inhibition by norepinephrine of 5-HT release from the somadendritic region of serotonergic neurons

• Published in: Brain research bulletin 2001-08, Vol.55 (6), p.761-765
• Main Authors: Kalsner, Stanley, Abdali, Syed Amir
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-Agonists - pharmacology; Adrenergic alpha-Antagonists - pharmacology; Animals; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Dendrites - drug effects; Dendrites - metabolism; Dose-Response Relationship, Drug; Electric Stimulation; Feedback - drug effects; Feedback - physiology; Feedback inhibition; Fluoxetine - analogs & derivatives; Fluoxetine - pharmacology; Fundamental and applied biological sciences. Psychology; Mesencephalon - drug effects; Mesencephalon - metabolism; Methiothepin - pharmacology; Neural Inhibition - drug effects; Neural Inhibition - physiology; Neurons - drug effects; Neurons - metabolism; Neurotransmitters; Norepinephrine; Norepinephrine - metabolism; Norepinephrine - pharmacology; Phenylephrine - pharmacology; Prazosin - pharmacology; Rabbits; Raphe Nuclei - drug effects; Raphe Nuclei - metabolism; Receptors, Adrenergic - drug effects; Receptors, Adrenergic - metabolism; Serotonergic nerves; Serotonin - metabolism; Serotonin Antagonists - pharmacology; Vertebrates: nervous system and sense organs; Yohimbine - pharmacology
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/S0361-9230(01)00567-6

Endogenous adrenergic drive regulates the firing rate of serotonergic neurons. However, advocates of feedback theory assert that 5-hydroxytryptamine (5-HT) released in the somatodendritic region of raphe neurons regulates both rate and release of 5-HT. Experiments were done to determine if the somatodendritic region might have receptors for norepinephrine that inhibit release of 5-HT independently of rate, as this would allow for discrete effects of norepinephrine on rate and release, even in the presence of functional feedback by 5-HT. The release of 5-HT at fixed frequencies of stimulation was substantially reduced when norepinephrine (1 and 3 × 10 −7 M) was present. Norepinephrine also inhibited the release of 3H-5-HT with delivery of a single stimulation pulse ruling out a remote action of the catecholamine. The α 1 antagonist prazosin did not modify the profile of norepinephrine inhibition. Further, the α 1 agonist phenylephrine had no effect on 3H-5-HT efflux. The α 2 antagonist yohimbine antagonized almost entirely the inhibition by norepinephrine at 1 Hz, and reduced it substantially at 3 Hz. Blockade of 5-HT 1 receptor sites with methiothepin did not reduce the inhibitory effect of norepinephrine on 3H-5-HT efflux. It is proposed that release of endogenous norepinephrine at synapses with 5-HT neurons could activate 5-HT neuron firing rate through α 1 receptors located at the soma and simultaneously short-circuit ongoing 5-HT feedback inhibition by inhibiting release through adrenergic alpha two receptors likely located at the dendrites.