Nicotine interferes with GABA-mediated inhibitory processes in mouse hippocampus.
Previous studies indicated that the excitatory effects of nicotine may be mediated via interference with GABAergic transmission. Here, several variants of the paired-pulse paradigm were employed to ascertain whether nicotine interferes with endogenous inhibitory circuits in the hippocampus. Nicotine attenuated the inhibition evoked by antidromic (alvear) stimulation in the CA1 region in a concentration-dependent manner (EC50 = 60-75 microM). This same phenomenon was also observed for the GABAA receptor antagonist bicuculline (0.1 microM). Orthodromic-orthodromic paired-pulse paradigms were found to be unsuitable for investigating the effects of epileptogenic agents such as nicotine and bicuculline on endogenous inhibition.
Freund
R K
RK
Institute for Behavioral Genetics, University of Colorado, Boulder 80309.
Luntz-Leybman
V
V
Collins
A C
AC
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D008811:Mice, Inbred DBA; D009538:Nicotine / Q000494:pharmacology*; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D005680:gamma-Aminobutyric Acid; D009538:Nicotine; D001640:Bicuculline