Intraseptal injection of GABA and benzodiazepine receptor ligands alters high-affinity choline transport in the hippocampus

Brain Res Bull. 1993;31(3-4):267-71. doi: 10.1016/0361-9230(93)90216-x.

Abstract

Injection of GABA and benzodiazepine (BDZ) agonists and antagonists into the medial septum produced bidirectional alterations in hippocampal high-affinity choline transport (HAChT). Male Sprague-Dawley rats were injected in the medial septum with either drug vehicle, a BDZ agonist, antagonist, or inverse agonist, or with a GABA-A or GABA-B agonist or antagonist and sacrificed 1 h later for assessment of HAChT in hippocampal synaptosomes. The GABA-A agonist muscimol, the GABA-B agonist baclofen, and the BDZ agonist chlordiazepoxide (CDP) produced dose-related decreases in HAChT 1 h following injection into the septum. The muscimol-induced decrease in HAChT was prevented by prior intraseptal injection of the GABA-A antagonist, bicuculline. Intraseptal injection of GABA-A (bicuculline) or GABA-B (2-hydroxysaclofen) antagonists did not alter HAChT, whereas the BDZ antagonist flumazenil (RO15,1788) and the BDZ inverse agonist methyl-beta-carboline-3-carboxylate (beta-CCM) increased this measure up to 30% in a dose-dependent manner. These results demonstrate that cholinergic neurons in the medial septum can be modulated in a bidirectional way through the pharmacological manipulation of GABA-A, GABA-B, and BDZ receptors. The potential functional and therapeutic consequences of these interactions are discussed.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Baclofen / administration & dosage
  • Baclofen / pharmacology
  • Brain
  • Carbolines / administration & dosage
  • Carbolines / pharmacology
  • Chlordiazepoxide / pharmacology
  • Choline / metabolism*
  • Convulsants / administration & dosage
  • Convulsants / pharmacology
  • Flumazenil / administration & dosage
  • Flumazenil / pharmacology
  • Hippocampus / drug effects
  • Hippocampus / enzymology
  • Hippocampus / metabolism*
  • Injections
  • Male
  • Muscimol / administration & dosage
  • Muscimol / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / drug effects*
  • Receptors, GABA-A / metabolism
  • Synaptosomes / metabolism
  • gamma-Aminobutyric Acid / administration & dosage
  • gamma-Aminobutyric Acid / pharmacology*

Substances

  • Carbolines
  • Convulsants
  • Receptors, GABA-A
  • Muscimol
  • Flumazenil
  • gamma-Aminobutyric Acid
  • Chlordiazepoxide
  • Acetylcholinesterase
  • Baclofen
  • beta-carboline-3-carboxylic acid methyl ester
  • Choline