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 [ 35 S]GTPγS binding stimulated by the 5‐HT 1A receptor agonist (+/–)‐8‐hydroxy‐2‐dipropyl‐aminotetralin hydrobromide (8‐OH‐DPAT; 1 µ m ). In BDNF (+/–) versus wild‐type (WT) mice, 5‐HT 1A receptor‐stimulated [ 35 S]GTPγS binding was significantly attenuated in the median raphe nucleus. There was a decrease in (+/–)8‐OH‐DPAT‐stimulated [ 35 S]GTPγS binding in the dorsal raphe, which did not reach statistical significance. In the hippocampus, 5‐HT 1A receptor–stimulated [ 35 S]GTPγS binding was significantly attenuated in BDNF (+/–) mice. 5‐HT 1A receptor–stimulated [ 35 S]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.