Genetic and pharmacological strategies identify a behavioral function of neuronal nicotinic receptors

Jerry A. Stitzel, Ying Lu, Melissa Jimenez, Theresa Tritto, Allan C. Collins

Research output: Contribution to journalArticlepeer-review

Abstract

The studies outlined here used pharmacological and genetic approaches to attempt to identify the nicotinic receptors that modulate nicotine-induced seizures. Full-blown clonic-tonic seizures were induced by intracerebroventricular (i.c.v.) injection of nicotine, the α4β2 selective agonist ABT-418 and the α7-selective GTS-21. Cytisine, which is a partial agonist at α4β2-type receptors, produced partial seizures. DHβE and MLA did not block nicotine-induced seizures. Instead, both antagonists caused seizures. Restriction fragment length polymorphisms (RFLPs) for the α7 receptor were identified in two inbred strains (C3H and DBA) that differ in sensitivity to nicotine-induced seizures. F2 mice derived from a C3H x DBA cross that were homozygous for the C3H variant of the α7 RFLP were more sensitive to nicotine-induced seizures than were F2 mice that were homozygous for the DBA RFLP. In a study that used RI strains derived from two selectively bred mouse lines (LS and SS), an association between sensitivity to nicotine-induced seizures and an RFLP associated with the α4 gene was found. These data support the assertion that both α4 and α7 receptor types are involved in modulating convulsions produced by nicotine. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)57-64
Number of pages8
JournalBehavioural Brain Research
Volume113
Issue number1-2
DOIs
StatePublished - Aug 2000

Keywords

  • Cytisine
  • Genetics
  • Nicotine
  • Nicotinic receptors
  • Seizure

ASJC Scopus subject areas

  • Behavioral Neuroscience

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