Comparison of the effects of M1 and M2 muscarinic receptor activation in the absence of GABAergic inhibition in immature rat hippocampal CA3 area.
We have reported previously that addition of carbachol (CCh, 25 microM) in the presence of the GABAA antagonist bicuculline (BMI, 10 microM), depresses evoked synaptic responses and significantly increases the frequency of spontaneous synchronous discharges in immature (postnatal days 10-20, P10-P20) hippocampus in vitro. The present experiments were designed in order to compare the activity of CCh with that of the selective muscarinic agonists McN-A-343 (M1 agonist) and oxotremorine-M (M2 agonist), in inducing the above-mentioned effects. Cholinergic agonists were tested in concentrations ranging from 2.5 nM to 5 microM and synaptic field potentials (evoked, spontaneous) were recorded from the CA3 pyramidal layer of hippocampal slices in the presence of BMI (10 microM). Depression of the evoked responses was measured as decrease (i) in their duration, (ii) in the number of population spikes/response, and (iii) in the amplitude of the first population spike of each sequence. Sigmoid dose-response curves were plotted, and the IC50s were calculated. For all three indexes, the profile of effectiveness was Oxotremorine-M>carbachol=McN-A-343. CCh and oxotremorine-M induced or increased the frequency of spontaneous synchronous discharges in the presence of BMI in a concentration-dependent manner. At the range of concentrations tested, McN-A-343 did not mimic this effect. In conclusion, our results suggest that M2 muscarinic receptors play a major role in both the depression of synaptic responses and the increase in the frequency of spontaneous synchronous discharges observed in the absence of GABAergic inhibition.
Psarropoulou
C
C
Dept of Physiology and Biophysics, Faculty of Medicine, University of Sherbrooke, Sherbrooke, QC, Canada. caterina@justine.umontreal.ca
Beaucher
J
J
Harnois
C
C
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology; D005071:Evoked Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000254:growth & development*; D066298:In Vitro Techniques; D018721:Muscarinic Agonists / Q000494:pharmacology*; D010095:Oxotremorine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000502:physiology*
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D010095:Oxotremorine; D002217:Carbachol; D001640:Bicuculline