Galanin/5-HT Receptor Interactions. A New Integrative Mechanism in the Control of 5-HT Neurotransmission in the Central Nervous System

Biochemical and functional evidence has been presented for the existence of bidirectional intramembrane interactions betweeen galanin receptors and 5-HT-1A receptors in the ventral limbic cortex, the thalamic midline nuclei and the hypothalamus. Galanin seems to reduce the sensitivity of 5-HT-1A receptors by reducing their affinity, while 5-HT-1A receptor activation leads to an increase in the sensitivity of the galanin receptors, probably by an increase in their affinity. These results are supported by neuroendocrine results obtained on serum prolactin and TSH levels after combined central and systemic administration of galanin and of the 5-HT-1A receptor agonist DPAT, respectively. Thus, the galanin receptor may be part of an intramembrane negative feedback system controlling the 5-HT-1A receptor. In areas of codistribution the galanin receptor alters the decoding of the 5-HT signal by selectively downregulating the 5-HT-1A receptor whereas the 5-HT-1B and the 5-HT-2 receptors do not appear to be altered in the ventral limbic cortex. However, evidence indicates that centrally administered galanin can markedly counteract 5-HT-2 receptor dependent behaviours such as headtwitches, induced by a 5-HT-2 receptor agonist.