Ethanol consumption and serotonin-1A (5-HT_1A) 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-HT_1A 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-HT_1A receptor agonist (+/-)-8-hydroxy-2-dipropyl-aminotetralin hydrobromide (8-OH-DPAT; 1 μM). In BDNF (+/-) versus wild-type (WT) mice, 5-HT_1A 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-HT_1A receptor-stimulated [³⁵S]GTPγS binding was significantly attenuated in BDNF (+/-) mice. 5-HT_1A receptor-stimulated [³⁵S]GTPγS binding was attenuated in the anterior cingulate cortex and lateral septum, although these reductions did not reach statistical significance. 5-HT_1A receptor number was not different between genotypes in any area of brain examined, suggesting that 5-HT_1A receptor function, specifically the capacity of the 5-HT_1A receptor to activate G proteins, is attenuated in BDNF (+/-) mice.