RT Journal Article
SR Electronic
T1 Local α-Bungarotoxin-Sensitive Nicotinic Receptors Modulate Hippocampal Norepinephrine Release by Systemic Nicotine
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 133
OP 139
VO 289
IS 1
A1 Yitong Fu
A1 Shannon G. Matta
A1 Burt M. Sharp
YR 1999
UL http://jpet.aspetjournals.org/content/289/1/133.abstract
AB Previous studies have shown that nicotinic receptors (NAChRs) accessible from the cerebral aqueduct of the brainstem mediate the hippocampal norepinephrine (NE) release induced by i.v. nicotine. The present study was designed to investigate the role of hippocampal NAChRs in this process. Nicotinic antagonists were microinjected or microdialyzed into the hippocampus (HP) before administering nicotine (0.09 mg/kg over 60 s, i.v.) to freely moving rats. α-Bungarotoxin (0.3 nmol by microinjection) blocked nicotine-induced hippocampal NE release by 47% (p < .05) and abolished the effect of 0.065 mg/kg nicotine. Methyllycaconitine (1.4–5.6 mM in the dialysate) inhibited the stimulatory effect of nicotine 0.09 mg/kg by 48 to 75% (p < .05). In contrast, mecamylamine (2.9–5.8 mM) and dihydro-β-erythroidine (7–14 mM) were completely ineffective. The role of hippocampal NAChRs was demonstrated further by selectively desensitizing these receptors before the systemic infusion of nicotine. To do so, the HP was pretreated with nicotine (0.1 mM) delivered through the microdialysis probe; this concentration was calculated to yield tissue concentrations similar to those produced by the systemic infusions of nicotine. Dialyzing this concentration of nicotine into the HP inhibited the NE response to i.v. nicotine by 34% (p < .05), and 1.0 mM nicotine reduced the response by 40%. These studies indicate that α-bungarotoxin-sensitive hippocampal NAChRs, probably containing α7 subunits, modulate hippocampal NE release because of systemic nicotine. The American Society for Pharmacology and Experimental Therapeutics