PMID: 11923419Mar 30, 2002Paper

Nicotinic acetylcholine receptors interact with dopamine in induction of striatal long-term depression

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
John G PartridgeDavid M Lovinger

Abstract

The dorsal striatum participates in motor function and stimulus-response or "habit" learning. Acetylcholine (ACh) is a prominent neurotransmitter in the striatum and exerts part of its actions through nicotinic cholinergic receptors. Activation of these receptors has been associated with the enhancement of learning and certainly is instrumental in habitual use of nicotine. Nicotinic receptors have also been suggested to be a possible therapeutic target for disorders of the basal ganglia. In this report we show that the activation of nicotinic acetylcholine receptors in the dorsal striatum contributes to dopamine (DA)- and activity-dependent changes in synaptic efficacy. High-frequency activation of glutamatergic synapses onto striatal neurons results in a long-term depression (LTD) of synaptic efficacy that is dependent on the activation of dopamine receptors. This stimulation also produces robust increases in extracellular dopamine concentration as well as strong activation of cholinergic striatal interneurons. Antagonists of nicotinic acetylcholine receptors inhibit striatal LTD. However, on coapplication of dopamine reuptake inhibitors with nicotinic receptor antagonists, activity-induced striatal LTD is restored. Dopamine r...Continue Reading

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