3-α-Chloro-imperialine, a potent blocker of cholinergic presynaptic modulation of glutamatergic afferents in the rat neostriatum

摘要: Abstract Cortico-thalamic glutamatergic afferents control neuronal activity in the neostriatum. Cholinergic interneurons modulate of medium spiny neurons through both pre- and post-synaptic actions via activation muscarinic receptors. The pre-synaptic modulation was analyzed electrophysiologically. transmitter release, induced by 4-AP, studied block paired pulse facilitation (PPF) different receptor antagonists analyzed. GABAA antagonist bicuculline isolated transmission. Muscarinic agonists decreased frequency random synaptic potentials 4-AP about 60% cases without changes input resistance (RN) neuron or mean amplitude events; indicating a presynaptic action. administration 1 μM carbachol 20 nM muscarine increased PPF. blocked this action with potency order: 3-α-chloroimperialine>4-DAMP>AFDX-116≥gallamine⪢pirenzepine. IC50’s for first three were (nM): 0.65, 1.1, 3.0. Their respective Hill coefficients were: 1.9, 1.4, 1.3. 3-α-Chloroimperialine reduced PPF almost completely. M3 M2 4-DAMP AFDX-116, given at saturating concentrations, consistently only part but had additive effects when together. These data are consistent existence receptors striatal afferents.