Inhibition of nicotine-induced hippocampal norepinephrine release in rats by alpha-conotoxins MII and AuIB microinjected into the locus coeruleus

Abstract

Hippocampal norepinephrine (NE) is secreted by neurons projecting from the locus coeruleus (LC) to the hippocampus; LC nicotinic receptors (NAchRs) are involved in the effects of systemic nicotine on this pathway. To clarify the NAchR subtypes, NAchR antagonists, termed α-conotoxins, were microinjected into the LC before nicotine; MII and AulB were used to assess the potential involvement of α3 β2 and α3 β4 subunit-containing NAchRs, respectively. Nicotine dose-dependently stimulated hippocampal NE release ( P<0.01). MII (>0.25 pmol) reduced the NE response to nicotine (67% decrease; P<0.05), as did AuIB (44% reduction by 25 pmol; P<0.05). Administered together, however, MII and AuIB were no more effective than MII. Thus, MII and AuIB are capable of interacting with NAchR subtypes other than those previously defined as α3 β2 and α3 β4, respectively. NAchRs containing both β2 and β4subunits may be involved.