Long-lasting enhancement of glutamatergic synaptic transmission by acetylcholine contrasts with response adaptation after exposure to low-level nicotine.
Attempts to mimic synaptic delivery of acetylcholine (ACh) with brief, repetitive pulses of high concentration ACh at synapses of medial habenula (MHN) and interpeduncular nucleus (IPN) neurons in vitro elicited temporally distinct facilitation and inhibition of glutamate secretion via nicotinic and muscarinic ACh receptor-mediated pathways, respectively. ACh-induced nicotinic facilitation was sustained for up to 2 hr, whereas muscarinic inhibition was transient. Prolonged exposure to nicotine inactivated nicotinic receptors selectively, thus decreasing the relative contribution of the facilitatory versus inhibitory influences of ACh. The net effect of ACh in modulating glutamatergic transmission at MHN-IPN synapses may be determined by pre-exposure to nicotine, because the drug appears to switch the balance between the facilitatory and inhibitory actions of ACh.
Girod
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Department of Anatomy, Center for Neurobiology and Behavior, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
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D000109:Acetylcholine / Q000494:pharmacology*; D000222:Adaptation, Physiological / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D019262:Habenula / Q000502:physiology; D008636:Mesencephalon / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011976:Receptors, Muscarinic / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D018698:Glutamic Acid; D009538:Nicotine; D000109:Acetylcholine