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, repe titive pulses of high concentration ACh at synapses of medial habenula (MHN ) and interpeduncular nucleus (IPN) neurons in vitro elicited temporally di stinct facilitation and inhibition of glutamate secretion via nicotinic and muscarinic ACh receptor-mediated pathways, respectively. ACh-induced nicot inic facilitation was sustained for up to 2 hr, whereas muscarinic inhibiti on was transient. Prolonged exposure to nicotine inactivated nicotinic rece ptors selectively, thus decreasing the relative contribution of the facilit atory versus inhibitory influences of ACh. The net effect of ACh in modulat ing glutamatergic transmission at MHN-IPN synapses may be determined by pre -exposure to nicotine, because the drug appears to switch the balance betwe en the facilitatory and inhibitory actions of ACh.