Bombesin stimulates dorsal raphe nucleus serotonergic neurons via a mechanism involving BB1 receptors

The involvement of serotonin (5-HT) in mood and appetite regulation is well established. This neurotransmitter is released from the neurons located in brainstem raphe nuclei. The excitability of the raphe 5-HT neurons, determining 5-HT neurotransmission, is regulated by various biomolecules, among them gastroenteric hormones, such as gastrin-releasing peptide (GRP). We aimed to examine the effects of the GRP homolog bombesin, and antagonist of bombesin BB1 receptor PD 176252, on the excitability of 5-HT neurons in in vivo conditions. In order to achieve its permeability through the blood-brain barrier, bombesin was fused to the cell-membrane transduction domain of the human immunodeficiency virus-type-1 Tat protein. We found that Tat-bombesin complex increased the firing activity of 5-HT neurons; PD 176252 had an opposite effect. GRP might thus regulate 5-HT neurotransmission via a mechanism involving BB1 receptors. BB1 ligands may therefore be used for the treatment of mood and eating disorders.