Presynaptic muscarinic modulation of nicotinic excitation in the rat neostriatum

In rat neostriatal slices, cholinergic agents were tested for their effects on endogenous ACh release and on electrical activity. ACh release was evoked by 25 mM K+ during two 5-min periods between which a slice was allowed to rest for 20 min; drugs were present during the second stimulation period. In the absence of a cholinesterase inhibitor, only Ch outflow was monitored. For the recording of electrical activity, intrastriatal stimulation evoked field potentials which were monitored in the absence and presence of drugs in the perfusate. Atropine (1-100 microM) increased endogenous ACh release by 32-91% and effective doses were 10-fold lower in the presence of a cholinesterase inhibitor. Atropine also increased the amplitudes of synaptic population spikes in the field potentials. The muscarinic agonists muscarine (100 microM) and oxotremorine (25 and 100 microM) decreased endogenous ACh release. Atropine (10 microM) blocked the depressant effect of muscarine (100 microM). Muscarine (100 microM-1 mM) and oxotremorine (10-100 microM) decreased the electrically evoked excitation in the rat neostriatal slices, and their effects were reversed by atropine. Only higher concentrations of nicotine (1 and 5 mM) decreased the synaptic population spikes, but potassium-stimulated Ch outflow was not affected. It is concluded that in the neostriatum presynaptic muscarinic receptors modulate nicotinic excitation since potassium-stimulated ACh release and intrinsically evoked synaptic excitation are influenced by muscarinic drugs in the same way.