In vivo interaction between serotonin and galanin type 1 and type 2 receptors in dorsal raphe: implication for limbic seizures

Neuropeptide galanin suppresses seizure activity in the hippocampus by inhibiting glutamatergic neurotransmission. Galanin may also modulate limbic seizures through interaction with other neurotransmitters in neuronal populations that project to the hippocampus. We examined the role of galanin receptors types 1 and 2 in the dorsal raphe in regulation serotonergic transmission and limbic seizures. Infusion of a mixed agonist of galanin receptors 1 and 2, galanin (1-29), into the dorsal raphe augmented the severity of limbic seizures both in rats and in wild type mice, and concurrently reduced serotonin concentration in dorsal raphe and in the hippocampus, measured by immunofluorescence, or HPLC. In contrast, injection of galanin 2 receptor agonist galanin (2-11), mitigated the severity of seizures in both species, and increased serotonin concentration in both areas. Injection of both galanin fragments into the dorsal raphe of galanin receptor 1 knockout mice exerted anticonvulsant effects. Both proconvulsant activity of galanin (1-29) and seizure suppression by galanin (2-11) were abolished in serotonin – depleted animals. Our data indicate that in the dorsal raphe, galanin 1 and 2 receptors modulate serotonergic transmission in a negative and a positive fashion respectively, and that these effects translate into either facilitation, or inhibition of limbic seizures.