Role of the medial septum cholinoceptors in anxiogenic-like effects of nicotine

Physiol Behav. 2013 Jul 2:119:103-9. doi: 10.1016/j.physbeh.2013.06.004. Epub 2013 Jun 13.


The medial septum which is extensively connected to the hippocampus is involved in cholinergic theta oscillation control as well as the anxiety related disorders. In the present study, we aimed to investigate the possible involvement of the medial septum cholinoceptors in the nicotine-induced anxiogenic-like behaviors in rats, using the elevated plus-maze (EPM) test. Intraperitoneal administration of nicotine at 0.6 and 0.8 mg/kg, decreased the open-arms time percentage (%OAT) and open-arms entries percentage (%OAE); indicating an anxiogenic-like response. Intra-medial septum microinjection of mecamylamine, a nicotinic acetylcholine receptor (nAChR) antagonist at the doses of 1-4 μg/rat, increased %OAT (4 μg/rat), suggesting an anxiolytic-like effect. This however, did not alter the anxiogenic-like response induced by the effective dose of nicotine (0.6 mg/kg). Moreover, co-administration of the subthreshold dose of mecamylamine (2 μg/rat) plus nicotine at the dose of 0.5 or 0.6 mg/kg, increased or decreased the anxiolytic-like behaviors, respectively. On the other hand, sole intra-medial septum infusion of atropine, a muscarinic acetylcholine receptor (mAChR) antagonist, induced an anxiolytic (0.05 μg/rat) and anxiogenic (0.25 μg/rat)-like effects, respectively. The dose of 0.05 μg/rat however, blocked the nicotine response. Furthermore, intra-medial septum microinjection of the highest dose of mecamylamine (4 μg/rat) plus nicotine (0.6 mg/kg) decreased the locomotor activity, while other treatments had no effect on this parameter. Our results suggested that, nicotine-induced anxiogenic-like behaviors may be mediated via the activation of cholinoceptors and possibly other receptor mechanism(s) in the medial septum.

Keywords: Anxiety; Atropine; Elevated plus-maze; Mecamylamine; Medial septum; Nicotine; Rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / chemically induced
  • Anxiety / physiopathology*
  • Atropine / administration & dosage
  • Atropine / pharmacology
  • Cholinergic Agonists / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Mecamylamine / administration & dosage
  • Mecamylamine / pharmacology
  • Microinjections
  • Muscarinic Antagonists / administration & dosage
  • Muscarinic Antagonists / pharmacology
  • Nicotine / pharmacology*
  • Nicotinic Antagonists / administration & dosage
  • Nicotinic Antagonists / pharmacology
  • Rats
  • Receptors, Cholinergic / physiology*
  • Septum of Brain / drug effects*
  • Septum of Brain / physiology


  • Cholinergic Agonists
  • Muscarinic Antagonists
  • Nicotinic Antagonists
  • Receptors, Cholinergic
  • Mecamylamine
  • Nicotine
  • Atropine