Memory improving actions of gabapentin in mice: possible involvement of central muscarinic cholinergic mechanism

Neurosci Lett. 2001 Oct 5;311(3):153-6. doi: 10.1016/s0304-3940(01)02181-4.

Abstract

Male CF-1 mice were tested 48 h after training on a one trial step-through inhibitory avoidance task. Immediately post-training, intraperitoneal (i.p.) injections of the antiepileptic gabapentin (1-(aminomethyl) cyclohexaneacetic acid) (GBP, 10 mg/kg) enhanced retention performance. The effect was prevented by atropine, a central muscarinic cholinergic receptor antagonist (0.5 mg/kg, i.p.) administered after training but 10 min prior to GBP treatment. In contrast, neither methylatropine (0.5 mg/kg, i.p.), a peripherally acting muscarinic receptor blocker, nor mecamylamine (5 mg/kg, i.p.) or hexamethonium (5 mg/kg, i.p.), two cholinergic nicotinic receptor antagonists, prevented the effects of post-training GBP on retention performance. Low subeffective doses of the central acting anticholinesterase physostigmine (35 mg/kg, i.p.) administered immediately after training, and GBP (5 mg/kg, i.p.), given 10 min after training, significantly enhanced retention performance. The effects of GBP (5 mg/kg, i.p.) were not influenced by the peripherally acting anticholinesterase neostigmine (150 mg/kg, i.p.). Considered together, these findings suggest a disinhibitory action of GBP on the activity of central muscarinic cholinergic mechanisms that are involved in memory consolidation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / pharmacology*
  • Acetylcholine / metabolism*
  • Amines*
  • Animals
  • Avoidance Learning / drug effects
  • Avoidance Learning / physiology
  • Brain / drug effects*
  • Brain / metabolism
  • Cholinergic Antagonists / pharmacology
  • Cholinesterase Inhibitors / pharmacology
  • Cyclohexanecarboxylic Acids*
  • Dose-Response Relationship, Drug
  • Drug Interactions / physiology
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Gabapentin
  • Male
  • Memory / drug effects*
  • Memory / physiology
  • Mice
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Receptors, Muscarinic / drug effects*
  • Receptors, Muscarinic / metabolism
  • gamma-Aminobutyric Acid*

Substances

  • Acetates
  • Amines
  • Cholinergic Antagonists
  • Cholinesterase Inhibitors
  • Cyclohexanecarboxylic Acids
  • Excitatory Amino Acid Antagonists
  • Receptors, Muscarinic
  • gamma-Aminobutyric Acid
  • Gabapentin
  • Acetylcholine