Ethanol consumption and serotonin-1A (5-HT1A) receptor function in heterozygous BDNF (+/-) mice

J. G. Hensler, E. E. Ladenheim, W. E. Lyons

Research output: Contribution to journalArticlepeer-review

112 Scopus citations

Abstract

Heterozygous brain-derived neurotrophic factor (BDNF) (+/-) mice display abnormalities in central serotonergic neurotransmission, develop decrements in serotonergic innervation of the forebrain, and exhibit enhanced intermale aggressiveness. As disturbances of serotonin neurotransmission are implicated in alcohol abuse and aggression, we have examined in BDNF (+/-) mice alcohol drinking behavior, as well as central 5-hydroxytryptamine (5-HT)1A receptor function at the level of 5-HT1A receptor-G protein interaction. BDNF (+/-) mice displayed increased ethanol intake in a two-bottle choice procedure. There was no difference in the preference ratio for non-alcoholic tastants (i.e. quinine or saccharin) between genotypes. In the brains of alcohol-naive mice, we measured [35S]GTPγS binding stimulated by the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-dipropyl-aminotetralin hydrobromide (8-OH-DPAT; 1 μM). In BDNF (+/-) versus wild-type (WT) mice, 5-HT1A receptor-stimulated [35S]GTPγS binding was significantly attenuated in the median raphe nucleus. There was a decrease in (+/-)8-OH-DPAT-stimulated [35S]GTPγS binding in the dorsal raphe, which did not reach statistical significance. In the hippocampus, 5-HT1A receptor-stimulated [35S]GTPγS binding was significantly attenuated in BDNF (+/-) mice. 5-HT1A receptor-stimulated [35S]GTPγS binding was attenuated in the anterior cingulate cortex and lateral septum, although these reductions did not reach statistical significance. 5-HT1A receptor number was not different between genotypes in any area of brain examined, suggesting that 5-HT1A receptor function, specifically the capacity of the 5-HT1A receptor to activate G proteins, is attenuated in BDNF (+/-) mice.

Original languageEnglish (US)
Pages (from-to)1139-1147
Number of pages9
JournalJournal of neurochemistry
Volume85
Issue number5
DOIs
StatePublished - Jun 2003

Keywords

  • Alcohol
  • Quantitative autoradiography
  • Two-bottle choice procedure
  • [S]GTPγS binding

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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