Abstract
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.
Footnotes
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Send reprint requests to: Burt M. Sharp, M.D., Department of Pharmacology, University of Tennessee, 874 Union Ave., Memphis, TN 38163. E-mail: Bsharp{at}utmem1.utmem.edu
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↵1 This work was supported by National Institutes of Health Grant DA03977 (to B.M.S.).
- Abbreviations:
- α-BTX
- α-bungarotoxin
- CSF
- cerebrospinal fluid
- DHβE
- dihydro-β-erythroidine
- HP
- hippocampus
- KRB
- Krebs-Ringer buffer
- LC
- locus coeruleus
- Mec
- mecamylamine
- MLA
- methyllycaconitine
- NAChRs
- nicotinic cholinergic receptors
- NE
- norepinephrine
- Received May 4, 1998.
- Accepted October 30, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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