Intraseptal injection of GABA and benzodiazepine receptor ligands alters high-affinity choline transport in the hippocampus.
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.
Department of Psychology, Rutgers University, New Brunswick, NJ 08903.
T J
TJ
Walsh
R W
RW
Stackman
D F
DF
Emerich
L A
LA
Taylor
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000494:pharmacology; D001921:Brain; D002243:Carbolines / Q000008:administration & dosage / Q000494:pharmacology; D002707:Chlordiazepoxide / Q000494:pharmacology; D002794:Choline / Q000378:metabolism*; D003292:Convulsants / Q000008:administration & dosage / Q000494:pharmacology; D005442:Flumazenil / Q000008:administration & dosage / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D007267:Injections; D008297:Male; D009118:Muscimol / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology*
D002243:Carbolines; D003292:Convulsants; D011963:Receptors, GABA-A; D009118:Muscimol; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D002707:Chlordiazepoxide; D000110:Acetylcholinesterase; D001418:Baclofen; C036150:beta-carboline-3-carboxylic acid methyl ester; D002794:Choline