Neuroanatomical and pharmacological evidence for a functional interaction between GABAergic and NPY-Y1 transmission in the amygdala of Y1R/LacZ transgenic mice.
Several lines of evidence indicate that GABA and neuropeptide Y (NPY) are functionally coupled and may interact in the regulation of fear- and anxiety-induced behavior. Neuroanatomical studies demonstrated that GABA and NPY coexist in neurons of the amygdaloid complex and that NPY may directly modulate the activity of GABAergic neurons by stimulating Y1 receptors. By using a transgenic mouse model harboring a construct comprising the murine Y1 receptor gene promoter fused to a lacZ reporter gene (Y1R/LacZ mice), we showed that long-term treatment with positive (diazepam or abecarnil) or negative (FG7142) modulators of GABAA receptor function induced a marked increase or decrease, respectively, in Y1 receptor gene expression in the amygdala. Furthermore, we demonstrated that a sustained increase in the brain concentrations of neuroactive steroids, induced by pharmacological treatment or by physiological conditions such as pregnancy, increases Y1 receptor gene expression in the amygdala of Y1R/LacZ transgenic mice, an effect similar to that induced by diazepam or abecarnil. These data provide evidence of a functional interaction between GABAergic and NPY-Y1 mediated transmission and suggest that neuroactive steroids may play an important role in the regulation of the NPY transmission. Finally, our data support a role of Y1 receptors in the behavioral and neuroendocrine responses to stress that, however, appears to be independent on the activation of the GABAergic system.
Eva
Carola
C
Dipartimento di Anatomia, Farmacologia e Medicina Legale, Sezione di Farmacologia, Università di Torino, Torino, Italy. carola.eva@unito.it
Mele
Paolo
P
Oberto
Alessandra
A
Panzica
GianCarlo
G
Pisu
Maria Giuseppina
MG
Serra
Mariangela
M
D000679:Amygdala / Q000033:anatomy & histology* / Q000502:physiology*; D000818:Animals; D017930:Genes, Reporter / Q000235:genetics; D007763:Lac Operon / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009478:Neuropeptide Y / Q000502:physiology*; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D009478:Neuropeptide Y; D005680:gamma-Aminobutyric Acid