Endogenous noradrenaline activates alpha 2-adrenoceptors on serotonergic nerve endings in human and rat neocortex

J Neurochem. 1993 Aug;61(2):474-80. doi: 10.1111/j.1471-4159.1993.tb02148.x.


Slices from human neocortex preincubated with [3H]serotonin ([3H]5-HT) were superfused and stimulated electrically to investigate whether the alpha 2-adrenoceptors on serotonergic terminals can be stimulated by endogenous noradrenaline (NA) released from neighboring noradrenergic fibers. The stimulation-evoked 3H overflow, representing action potential-induced, exocytotic release of 5-HT, was depressed by the NA uptake blocker (+)-oxaprotiline. Rauwolscine (a mixed alpha 2-adrenoceptor antagonist/5-HT autoreceptor agonist) or phentolamine [a combined alpha-adrenoceptor/5-HT autoreceptor antagonist; the latter drug in the presence of (+)-oxaprotiline] enhanced the release when the 5-HT autoreceptors had previously been blocked by metitepine. Under hypothermia the release of 5-HT was found to be decreased and that of NA to be increased; under these conditions idazoxan (an alpha 2-adrenoceptor antagonist) enhanced the release of 5-HT. In neocortex slices from rats (+)-oxaprotiline similarly depressed the release of 5-HT (measured with the same methods) as in human tissue. When rats were pretreated with 6-hydroxydopamine, the inhibitory effect of exogenous NA on 5-HT release was increased, and in slices from rats pretreated with desipramine, it was decreased. In conclusion, alpha 2-heteroreceptors can be activated by endogenous NA released from neighboring noradrenergic fibers. Because regulatory processes analogous to those in rats probably occur in humans as well, an up- or down-regulation of alpha 2-heteroreceptors in depressed patients with a (pathological) decrease or a (therapeutic) enhancement of the noradrenergic neurotransmission may also be assumed to occur.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Adult
  • Aged
  • Animals
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiology*
  • Cold Temperature
  • Electric Stimulation
  • Exocytosis
  • Female
  • Humans
  • In Vitro Techniques
  • Male
  • Maprotiline / analogs & derivatives
  • Maprotiline / pharmacology
  • Middle Aged
  • Nerve Endings / physiology*
  • Norepinephrine / pharmacology
  • Norepinephrine / physiology*
  • Phentolamine / pharmacology
  • Rats
  • Receptors, Adrenergic, alpha / physiology*
  • Serotonin / physiology*
  • Yohimbine / pharmacology


  • Receptors, Adrenergic, alpha
  • Maprotiline
  • Yohimbine
  • Serotonin
  • hydroxymaprotilin
  • Norepinephrine
  • Phentolamine