Release of [3H]-noradrenaline from rat hippocampal synaptosomes by nicotine: mediation by different nicotinic receptor subtypes from striatal [3H]-dopamine release

Br J Pharmacol. 1996 Feb;117(4):595-606. doi: 10.1111/j.1476-5381.1996.tb15232.x.


1. The aim of the present experiment was to characterize nicotine-evoked [3H]-noradrenaline ([3H]-NA) release from rat superfused hippocampal synaptosomes, using striatal [3H]-dopamine release for comparison. 2. (-)-Nicotine, cytisine, DMPP and acetylcholine (ACh) (with esterase inhibitor and muscarinic receptor blocker) increased NA release in a concentration-dependent manner (EC50 6.5 microM, 8.2 microM, 9.3 microM, and 27 microM, respectively) with similar efficacy. 3. Nicotine released striatal dopamine more potently than hippocampal NA (EC50 0.16 microM vs. 6.5 microM). (+)-Anatoxin-a also increased dopamine more potently than NA (EC50 0.05 microM vs. 0.39 microM), and maximal effects were similar to those of nicotine. Isoarecolone (10-320 microM) released dopamine more effectively than NA but a maximal effect was not reached. (-)-Lobeline (10-320 microM) evoked dopamine release, but the effect was large and delayed with respect to nicotine; NA release was not increased but rather depressed at high concentrations of lobeline. High K+ (10 mM) released and NA to similar extents. 4. Addition of the 5-hydroxytryptamine (5-HT) reuptake blocker, citalopram (1 microM) to hippocampal synaptosomes affected neither basal NA release nor nicotine-evoked release. 5. The nicotinic antagonist, mecamylamine (10 microM), virtually abolished NA and dopamine release evoked by high concentrations of nicotine, ACh, cytisine, isoarecolone, and anatoxin-a. Although NA release evoked by DMPP (100 microM) was entirely mecamylamine-sensitive, DMPP-evoked dopamine release was only partially blocked. Dopamine release evoked by lobeline (320 microM) was completely mecamylamine-insensitive. 6. The nicotinic antagonists dihydro-beta-erythroidine and methyllycaconitine inhibited nicotine-evoked dopamine release approximately 30 fold more potently than NA release. In contrast, the antagonist chlorisondamine, displayed a reverse sensitivity, whereas trimetaphan and mecamylamine did not preferentially block either response. None of these antagonists, given at a high concentration, significantly altered release evoked by high K+. 7. Blockade of nicotine-evoked transmitter release by methyllycaconitine and dihydro-beta-erythroidine was surmounted by a high concentration of nicotine (100 microM), but blockade by mecamylamine, chlorisondamine, and trimetaphan was insurmountable. 8. Nicotine-evoked NA release was unaffected by tetrodotoxin, whereas veratridine-evoked NA release was virtually abolished. 9. We conclude that presynaptic nicotinic receptors associated with striatal dopamine and hippocampal NA terminals differ pharmacologically. In situ hybridization studies suggest that nigrostriatal dopaminergic neurones express mainly alpha 4, alpha 5, and beta 2 nicotinic cholinoceptor subunits, whereas hippocampal-projecting noradrenaline (NA) neurones express alpha 3, beta 2 and beta 4 subunits. Pharmacological comparisons of recombinant receptors suggest that release of hippocampal NA may be modulated by receptors containing alpha 3 and beta 4 subunits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Alkaloids / pharmacology
  • Animals
  • Azocines
  • Bacterial Toxins / pharmacology
  • Citalopram / pharmacology
  • Corpus Striatum / metabolism*
  • Cyanobacteria Toxins
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • In Vitro Techniques
  • Male
  • Marine Toxins / pharmacology
  • Microcystins
  • Nicotine / pharmacology*
  • Nicotinic Agonists / pharmacology
  • Nicotinic Antagonists / pharmacology
  • Norepinephrine / metabolism*
  • Potassium / metabolism
  • Quinolizines
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Nicotinic / classification
  • Receptors, Nicotinic / physiology*
  • Serotonin Antagonists / pharmacology
  • Synaptosomes / drug effects*
  • Synaptosomes / metabolism
  • Tetrodotoxin / pharmacology
  • Tritium
  • Tropanes


  • Alkaloids
  • Azocines
  • Bacterial Toxins
  • Cyanobacteria Toxins
  • Marine Toxins
  • Microcystins
  • Nicotinic Agonists
  • Nicotinic Antagonists
  • Quinolizines
  • Receptors, Nicotinic
  • Serotonin Antagonists
  • Tropanes
  • Citalopram
  • Tritium
  • Tetrodotoxin
  • cytisine
  • Nicotine
  • anatoxin a
  • Acetylcholine
  • Potassium
  • Norepinephrine