In vivo interaction between serotonin and galanin receptors types 1 and 2 in the dorsal raphe: implication for limbic seizures.
The 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 (DR) in the regulation of serotonergic transmission and limbic seizures. Infusion of a mixed agonist of galanin receptors types 1 and 2 [galanin (1-29)] into the DR augmented the severity of limbic seizures in both rats and wild-type mice and concurrently reduced serotonin concentration in the DR and hippocampus as measured by immunofluorescence or HPLC. In contrast, injection of the galanin receptor type 2 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 DR of galanin receptor type 1 knockout mice exerted anticonvulsant effects. Both the 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 DR, galanin receptors types 1 and 2 modulate serotonergic transmission in a negative and a positive fashion, respectively, and that these effects translate into either facilitation or inhibition of limbic seizures.
Mazarati
Andrey M
AM
Department of Pediatrics, Division of Pediatric Neurology, D. Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA. mazarati@ucla.edu
Baldwin
Roger A
RA
Shinmei
Steve
S
Sankar
Raman
R
D000818:Animals; D002452:Cell Count / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000009:adverse effects; D004569:Electroencephalography / Q000379:methods; D019004:Galanin / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009638:Norepinephrine / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044091:Receptor, Galanin, Type 1 / Q000819:agonists / Q000172:deficiency / Q000378:metabolism*; D044092:Receptor, Galanin, Type 2 / Q000819:agonists / Q000378:metabolism*; D012640:Seizures / Q000209:etiology / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology; D010133:p-Chloroamphetamine / Q000494:pharmacology
D010446:Peptide Fragments; D044091:Receptor, Galanin, Type 1; D044092:Receptor, Galanin, Type 2; D018490:Serotonin Agents; C434734:galanin (2-11)-amide; D012701:Serotonin; D010133:p-Chloroamphetamine; D019004:Galanin; D009638:Norepinephrine