Muscarinic agonist carbachol depresses excitatory synaptic transmission in the rat basolateral amygdala in vitro.
Intracellular recordings in slice preparations of the basolateral amygdala were used to test which excitatory amino acid receptors mediate the excitatory postsynaptic potentials due to stimulation of the external capsule. These recordings were also used to examine the action of muscarinic agonists on the evoked excitatory potentials. Intracellular recordings from amygdaloid pyramidal neurons revealed that carbachol (2-20 microM) suppressed, in a dose-dependent manner, excitatory postsynaptic responses evoked by stimulation of the external capsule (EC). This effect was blocked by atropine. The estimated effective concentration to produce half-maximal response (EC(50)) was 6.2 microM. Synaptic suppression was observed with no changes in the input resistance of the recorded cells, suggesting a presynaptic mechanism. In addition, the results obtained using the paired-pulse protocol provided additional support for a presynaptic action of carbachol. To identify which subtype of cholinergic receptors were involved in the suppression of the EPSP, four partially selective muscarinic receptor antagonists were used at different concentrations: pirenzepine, a compound with a similar high affinity for muscarinic M1 and M4 receptors; gallamine, a noncompetitive antagonist for M2; methoctramine, an antagonist for M2 and M4; and 4-diphenylacetoxy-N-methylpiperidine, a compound with similar high affinity for muscarinic receptors M1 and M3. None of them independently antagonized the suppressive effect of carbachol on the evoked EPSP completely, suggesting that more than one muscarinic receptor subtype is involved in the effect. These experiments provide evidence that in the amygdala muscarinic agonists block the excitatory synaptic response, mediated by glutamic acid, by acting on several types of presynaptic receptors.
Yajeya
J
J
Departamento de Fisiología y Farmacología, Facultad de Medicina, Instituto de Neurociencias de Castilla y León, Universidad de Salamanca, Salamanca, Spain. yajeya@gugu.usal.es
De La Fuente
A
A
Criado
J M
JM
Bajo
V
V
Sánchez-Riolobos
A
A
Heredia
M
M
D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D005260:Female; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology
D018679:Cholinergic Agonists; D011976:Receptors, Muscarinic; D002217:Carbachol