title: Regional densities of benzodiazepine sites in the CNS of alcohol-naive P and NP rats.
abstract: The regional densities of benzodiazepine (BDZ) recognition sites coupled to GABAA receptors were studied in ethanol-naive alcohol-preferring (P) and -nonpreferring (NP) lines of rats by using quantitative autoradiography to measure the amount of 2 nM [3H]flunitrazepam (FNZ) binding in the absence and presence of 100 microM GABA. Lower values (p < 0.025) for [3H]FNZ binding (in the absence of GABA) were observed in the prefrontal cortex, layer 4 of the parietal cortex, and the nucleus accumbens shell of the P relative to the NP line. GABA significantly (p < 0.025) stimulated [3H]FNZ binding in all 50 central nervous system regions examined in both the P and the NP rats. The largest percent increases (190-220%) were observed in the prefrontal, cingulate, frontal, and parietal cortices; shell and core nucleus accumbens; caudate putamen; dorsal lateral, intermediate lateral, ventral lateral, and medial septal nuclei; and lateral hypothalamus. In several layers of the frontal and parietal cortices, a 25-30% greater net or percent increase (p < 0.025) in GABA-enhanced [3H]FNZ binding was observed in the P rats compared with the NP rats. In contrast, lower net or percent increases (p < 0.025) in GABA-enhanced [3H]FNZ binding were found in the entorhinal cortex, the mediodorsal thalamus, and the dorsal CA3 area and middle dentate gyrus of the posterior hippocampus of the P line relative to the NP line. The present findings suggest that there are innate regional differences between P and NP rats in the densities and/or affinities of BDZ recognition sites and in the coupling between the GABAA and BDZ binding sites.
authors.affiliation: Department of Psychiatry, Indiana University School of Medicine, Indianapolis, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Thielen
authors.forename: W J
authors.initials: WJ
authors.lastname: McBride
authors.forename: E
authors.initials: E
authors.lastname: Chernet
authors.forename: L
authors.initials: L
authors.lastname: Lumeng
authors.forename: T K
authors.initials: TK
authors.lastname: Li
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001569:Benzodiazepines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005445:Flunitrazepam / Q000378:metabolism; D008297:Male; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam