Abstract

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) neuronsin 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.