Muscarinic agonist carbachol depresses excitatory synaptic transmission inthe 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 excitat ory postsynaptic potentials due to stimulation of the external capsule. The se recordings were also used to examine the action of muscarinic agonists o n the evoked excitatory potentials. Intracellular recordings from amygdaloi d pyramidal neurons revealed that carbachol (2-20 mu M) suppressed, in a do se-dependent manner, excitatory postsynaptic responses evoked by stimulatio n of the external capsule (EC). This effect was blocked by atropine. The es timated effective concentration to produce half-maximal response (EC50) was 6.2 mu M. Synaptic suppression was observed with no changes in the input r esistance of the recorded cells, suggesting a presynaptic mechanism. In add ition, the results obtained using the paired-pulse protocol provided additi onal support for a presynaptic action of carbachol. To identify which subty pe of cholinergic receptors were involved in the suppression of the EPSP, f our partially selective muscarinic receptor antagonists were used at differ ent concentrations: pirenzepine, a compound with a similar high affinity fo r muscarinic M1 and M4 receptors; gallamine, a noncompetitive antagonist fo r M2; methoctramine, an antagonist for M2 and M4; and 4-diphenylacetoxy-N-m ethylpiperidine, a compound with similar high affinity for muscarinic recep tors M1 and M3. None of them independently antagonized the suppressive effe ct of carbachol on the evoked EPSP completely, suggesting that more than on e muscarinic receptor subtype is involved in the effect. These experiments provide evidence that in the amygdala muscarinic agonists block the excitat ory synaptic response, mediated by glutamic acid, by acting on several type s of presynaptic receptors. (C) 2000 Wiley-Liss, Inc.