Ethanol consumption and serotonin-1A (5-HT1A) receptor function in heterozygous BDNF (+/-) mice.
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]GTP gamma S binding stimulated by the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-dipropyl-aminotetralin hydrobromide (8-OH-DPAT; 1 microM). In BDNF (+/-) versus wild-type (WT) mice, 5-HT1A receptor-stimulated [35S]GTP gamma S binding was significantly attenuated in the median raphe nucleus. There was a decrease in (+/-)8-OH-DPAT-stimulated [35S]GTP gamma S binding in the dorsal raphe, which did not reach statistical significance. In the hippocampus, 5-HT1A receptor-stimulated [35S]GTP gamma S binding was significantly attenuated in BDNF (+/-) mice. 5-HT1A receptor-stimulated [35S]GTP gamma S 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.
Hensler
J G
JG
Department of Pharmacology, University of Texas Health Science Center - San Antonio, San Antonio, Texas 78229-3900, USA. hensler@uthscsa.edu
Ladenheim
E E
EE
Lyons
W E
WE
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000428:Alcohol Drinking / Q000235:genetics; D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency* / Q000235:genetics; D002755:Choice Behavior / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000493:pharmacokinetics; D006579:Heterozygote; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012646:Self Administration; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D019208:Brain-Derived Neurotrophic Factor; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000431:Ethanol; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D019204:GTP-Binding Proteins