title: Receptor subtype-dependent galanin actions on gamma-aminobutyric acidergic neurotransmission and ethanol responses in the central amygdala.
abstract: The neuropeptide galanin and its three receptor subtypes (GalR1-3) are expressed in the central amygdala (CeA), a brain region involved in stress- and anxiety-related behaviors, as well as alcohol dependence. Galanin also has been suggested to play a role in alcohol intake and alcohol dependence. We examined the effects of galanin in CeA slices from wild-type and knockout (KO) mice deficient of GalR2 and both GalR1 and GalR2 receptors. Galanin had dual effects on gamma-aminobutyric acid (GABA)-ergic transmission, decreasing the amplitudes of pharmacologically isolated GABAergic inhibitory postsynaptic potentials (IPSPs) in over half of CeA neurons but augmenting IPSPs in the others. The increase in IPSP size was absent after superfusion of the GalR3 antagonist SNAP 37889, whereas the IPSP depression was absent in CeA neurons of GalR1 × GalR2 double KO and GalR2 KO mice. Paired-pulse facilitation studies showed weak or infrequent effects of galanin on GABA release. Thus, galanin may act postsynaptically through GalR3 to augment GABAergic transmission in some CeA neurons, whereas GalR2 receptors likely are involved in the depression of IPSPs. Co-superfusion of ethanol, which augments IPSPs presynaptically, together with galanin caused summated effects of ethanol and galanin in those CeA neurons showing galanin-augmented IPSPs, suggesting the two agents act via different mechanisms in this population. However, in neurons showing IPSP-diminishing galanin effects, galanin blunted the ethanol effects, suggesting a preemptive effect of galanin. These findings may increase understanding of the complex cellular mechanisms that underlie the anxiety-related behavioral effects of galanin and ethanol in CeA.
authors.affiliation: Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Michal
authors.initials: M
authors.lastname: Bajo
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Madamba
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Lu
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Sharkey
authors.forename: Tamas
authors.initials: T
authors.lastname: Bartfai
authors.forename: George Robert
authors.initials: GR
authors.lastname: Siggins
mesh_terms: D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D001007:Anxiety / Q000209:etiology; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D059330:GABAergic Neurons / Q000187:drug effects; D019004:Galanin / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013315:Stress, Psychological / Q000209:etiology; D005680:gamma-Aminobutyric Acid / Q000187:drug effects
chemical_list: C510288:1-phenyl-3-((3-(trifluoromethyl)phenyl)imino)-1H-indol-2-one; D002492:Central Nervous System Depressants; D007211:Indoles; D018019:Receptors, Corticotropin-Releasing Hormone; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D019004:Galanin