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Bargas, J; Galarraga, E; Hernandez-Echeagaray, E (1998)

3-ALPHA-CHLORO-IMPERIALINE, A POTENT BLOCKER OF CHOLINERGIC PRESYNAPTIC MODULATION OF GLUTAMATERGIC AFFERENTS IN THE RAT NEOSTRIATUM

NEUROPHARMACOLOGY 37(12):1493-1502
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Cortico-thalamic glutamatergic afferents control neuronal activity in the neostriatum. Cholinergic interneurons modulate the activity of medium spiny neurons through both pre- and post-synaptic actions via the activation of muscarinic receptors. The muscarinic pre-synaptic modulation was analyzed electrophysiologically. The transmitter release, induced by 4-AP, was studied and the block of paired pulse facilitation (PPF by different muscarinic receptor antagonists was analyzed. The GABA(A) antagonist bicuculline isolated the glutamatergic transmission. Muscarinic agonists decreased the frequency of random synaptic potentials induced by 4-AP in about 60% of the cases without changes in input resistance (R-N) of the post-synaptic neuron or in the mean amplitude of the synaptic events; indicating a presynaptic: action. The administration of both 1 mu M carbachol or 20 nM muscarine increased PPF. Muscarinic receptor antagonists blocked this action with a potency order : 3-alpha-chloroimperialine > 4-DAMP > AFDX-116 greater than or equal to gallamine much greater than pirenzepine. The IC50's for the first three antagonists were (nM): 0.65, 1,1, and 3.0. Their respective Hill coefficients were: 1.9, 1.4, and 1.3. 3-alpha-Chloroimperialine reduced the PPF almost completely. The M-3 and the M-2 muscarinic receptor antagonists 4-DAMP and AFDX-116? given at saturating concentrations, consistently blocked only a part of the PPF but had additive effects when given together, These data are consistent with the existence of both M-2 and M-3 muscarinic receptors in striatal glutamatergic afferents. (C) 1998 Elsevier Science Ltd. All rights reserved.